Dissociation of hyperreninemia and renal prostaglandin synthesis in the adrenalectomized rat

The aim of this study was to determine whether hyperreninemia in the adrenalectomized (ADX) rat is dependent on renal prostaglandin synthesis, as has been suggested for two other hyperreninemic conditions, Bartter's syndrome and chronic liver disease.Plasma renin concentration (PRC) in anesthetized, ADX rats was significantly increased (Δ +480%; p < 0.001) compared to sham-operated controls. , indomethacin (10 mg/kg i.v.) significantly reduced PRC of anesthetized, ADX rats after both 45 min (Δ −34%; p < 0.05) and 90 min (Δ −47%; p < 0.05). renin release from renal cortical slices of ADX rats was also significantly greater (Δ +130%; p < 0.05) than from sham-operated control cortical slices. Renin release from cortical slices of ADX rats given dexamethasone (10 μg/kg/day) for 4 days prior to sacrifice did not differ from sham-operated control values.Prostaglandin E₂ (PGE₂) release from cortical slices of ADX rats did not differ significantly from controls. However, PGE₂ synthesis in glomeruli microdissected from ADX rats was significantly increased (Δ +110%; p < 0.001) compared to controls. PGE₂ synthesis in glomeruli of dexamethasone-treated ADX rats remained significantly elevated compared to controls. Ibuprofen (10⁻⁶ M) decreased PGE₂ synthesis in cortical slices by 80%. However, prostaglandin synthesis inhibition had no effect on renin release from either ADX or control renal cortical slices.These results suggest that despite increased glomerular synthesis, prostaglandins do not directly influence renin release in the ADX rat.     

Alleviation of free radical mediated oxidative and genotoxic effects of cadmium by farnesol in Swiss albino mice

Abstract

Farnesol is an isoprenoid found in essential oils of ambrette seeds, citronella and in various aromatic plants. Exposure to cadmium from various sources affects the renal system adversely and Cd is an established genotoxic agent. In the present study, we evaluated the antigenotoxic and antioxidant efficacy of farnesol against cadmium chloride (CdCl₂)-induced renal oxidative stress and genotoxicity in Swiss albino mice. Single, intraperitoneal doses of CdCl₂(5 mg/kg body weight) for 24 h resulted in a significant (P < 0.001) increase in chromosomal aberration and micronuclei formation. The oral administration of farnesol at two doses (1% and 2% per kg body weight) for seven consecutive days showed significant (P < 0.05) suppression of the genotoxic effects of CdCl₂ in the modulator groups. To study the mechanism by which farnesol exerts its antigenotoxic potential, enzymes involved in metabolism and detoxification were estimated. CdCl₂ intoxication adversely affected the renal antioxidant armory and increased TBARS formation and xanthine oxidase levels significantly (P < 0.001). Farnesol showed a significant (P < 0.001) recovery in antioxidant status viz, GSH content (and its dependent enzymes) and catalase activity. Farnesol pretreatment in CdCl₂-intoxicated mice showed marked (P < 0.001) suppression of TBARS' formation and XO activity. Our results support the conclusion that the anticlastogenic effect of farnesol could be due to restoration of antioxidants and inhibition of oxidative damage.     

Effect of harvest time of red and white clover silage on chewing activity and particle size distribution in boli,rumen content and faeces in cows

The study examined the effects of harvest time of red and white clover silage on eating and ruminating activity and particle size distribution in feed boli, rumen content and faeces in cows. The clover crops were harvested at two stages of growth and ensiled in bales. Red clover crops had 36% and 45% NDF in dry matter (DM) at early (ER) and late (LR) harvest, respectively, and the white clover crops had 19% and 29% NDF in DM at the early (EW) and late (LW) harvest, respectively. The silages were fed restrictively (80% of ad libitum intake) twice daily to four rumen cannulated non-lactating Jersey cows (588 ± 52 kg) in a 4 × 4 Latin square design. Jaw movements (JM) were recorded for 96 h continuously. Swallowed boli, rumen mat, rumen fluid and faeces samples were collected, washed in nylon bags (0.01 mm pore size) and freeze-dried before dry sieving through 4.750, 2.360, 1.000, 0.500, 0.212 and 0.106 mm into seven fractions. The length (PL) and width (PW) values of rumen and faeces particles within each fraction were measured by use of image analysis. The eating activity (min/kg DM intake; P < 0.05) was higher in LR compared with the other treatments. The eating activity (min/kg NDF intake; P < 0.05) was affected by clover type with highest values for white clover silage. The mean ruminating time (min/kg DM), daily ruminating cycles (P < 0.001) and JM during ruminating (P < 0.05) were affected by treatment with increasing values at later harvest time. The proportion of washed particle DM of total DM in boli (P < 0.001), rumen mat (P < 0.001), rumen fluid (P < 0.01) and faeces was (P < 0.001) highest by feeding LR. There were identified two peaks (modes 1 and 2) on the probability density distribution (PDF) of PW values of rumen mat and faeces, but only one peak (mode 1) for PL values. There was no difference in the mean and mode 1 PW and PL value in rumen mat between the four treatments. The mean PL, mode PL, mode 2 PW and mean PW in faeces were highest for LR (P < 0.05). The mean particle size in boli measured by sieving was higher at white clover compared with red clover treatments (P < 0.001) and the highest value in faeces was found in LR (P < 0.01). The two peaks on PDF for width values of rumen mat and faeces particles are most likely related to the leaves and the stems/petioles. In conclusion, the mean total chewing activity per kg DM was lowest for the white clover silage and increased for both silages due to later harvest time. The mean particle size in boli was smallest for LR, whereas the mean PL and PW in faeces were highest for the LR.     

Cardiovascular effects of Atenolol, Scopolamine and their combination on healthy men in Finnish sauna baths

Indicators of cardiovascular strain were studied in 12 healthy young men under the influence of drugs affecting the autonomic nervous system during the course of taking a sauna bath. There were four bath sessions: one without a drug (control) and three with drug pretreatment (Atenolol 50 mg or Scopolamine 0.3 mg or their combination taken orally 2 h before the bath). The time spent in the hot room depended on the subjective rating of heat stress. Its mean duration at a temperature of 88°C (dry bulb) was 22 (range 14–33) min and did not differ significantly among the sessions. In the Atenolol experiment the mean resting heart rate before the bath was significantly lower (P < 0.001, ANOVA of repeated measures) than in the other experiments. The increase in heart rate per minute of heat exposure was significantly lower (P < 0.001) in the Atenolol experiment and higher (P=0.017) in the Scopolamine experiment than in the other experiments. The systolic blood pressure increased more slowly (P=0.004) and the diastolic pressure decreased less (P=0.02) in the Atenolol experiment than in the other experiments. Heart rate and blood pressure returned to their initial levels during the 30-min recovery after the heat exposure. The plasma noradrenaline concentrations increased approximately twofold during all of the bath sessions, whereas the plasma adrenaline and serum thromboxane B2 concentrations showed no consistent alterations. A small oral dose of Scopolamine alone or in combination with Atenolol produced no marked cardiovascular strain in healthy men during a sauna bath.     

Effect of starch application into the proximal duodenum of ruminants on starch digestibility in the small and total intestine

Four Slovakian Black‐and‐white bulls (LW 410 ± 12 kg; Exp. 1) and four Slovakian Black‐and‐white non lactating dairy cows (LW 475 ± 14 kg; Exp. 2) with permanent ruminal cannulas, duodenal T‐cannulas and ileal re‐entrant cannulas were used in a 4 × 4 Latin square design to determine the postruminal capacity of starch digestion.

In Exp. 1 bulls received 5.4 kg DM from corn silage and 3.6 kg DM from alfalfa hay, in Exp. 2 cows consumed only 2.1 kg DM corn silage and 1.9 kg DM alfalfa hay. Additionally, either 750 or 1500 g (Exp. 1) or resp. 1000 or 2000 g (Exp. 2) gelatinized corn or wheat starch per animal and day were applied as pulse doses or as infusion into the proximal duodenum.

In both experiments the duodenal and ileal nutrient flow, as well as the faecal excretion without starch application, were measured in a pre‐period. After starting starch application ileal digesta and faeces were sampled over 120 h after 9 or 23 days of adaptation respectively. Cr₂O₃ was used as a flow marker.

It was shown, that the capacity of starch utilisation in the small intestine was limited. The effect of different doses of bypass‐starch was more pronounced than the effect of different starch sources. Starch digestibility decreased with increasing amounts of starch in the intestine (Exp. 1: corn starch: from 74.3 to 68.0%, P < 0.001; wheat starch: from 76.7 to 67.4%, P <0.001; Exp. 2: corn starch: from 71.4 to 50.3%, P <0.001; wheat starch: from 73.8 to 53.1%, P <0.001). Corn starch was 0.6 to 2.4% units (P <0.05) and 2.4 to 2.8% units (P < 0.001) less digested than wheat starch in Exp. 1 and Exp. 2, respectively.

The decreased starch digestibility in the small intestine with increasing amounts of starch at the duodenum was not totally compensated in the large intestine. The starch digestibility in the total intestine for the low and high amounts of applied starch was: 83.7 and 81.0% (P < 0.001, corn starch, Exp. 1), 86.0 and 81.7% (P < 0.001, wheat starch, Exp. 1), 95.5 and 79.1% (P < 0.001, corn starch, Exp. 2), 99.8 and 81.7% (P < 0.001, wheat starch, Exp. 2).

Corn starch was 0.7 to 2.3% units (P <0.001) and 2.6 to 4.3% units (P <0.001) less digested than wheat starch in Exp. 1 and Exp. 2, respectively.

Model calculations were used to quantify the efficiency of starch utilisation. The recommended maximal amount of bypass‐starch is supposed to be 1.3 to 1.8 kg per animal and day.     

Reactivity of isolated toad aortic rings to angiotension II: the role of nitric oxide

Little is known about the vascular actions of angiotensin II (Ang II) and nitric oxide (NO) in Amphibia. This study investigated (1) Ang II contractility, (2) NO concentrations, and (3) correlations between Ang II contractility, NO concentration and mean arterial pressure (MAP) in isolated Bufo arenarum toad aortic rings. Contractility was measured in isometric conditions, NO concentrations were determined by the Griess reaction, and MAP was determined by a direct method. In isolated toad aortic rings, Ang II produced a contractile response (292.7 ± 89.2 mg; n = 20). Furthermore, a contractile response to norepinephrine (NE) was also obtained. A significant correlation between both the Ang II and NE contractile responses was found (r = 0.89; n = 11; P < 0.01). Administration of Ang II increased MAP values (Basal 16.8 ± 1.7; n = 19 vs. Ang II 28.4 ± 1.8 mmHg; n = 19; P < 0.001), and the increase of MAP by Ang II was positively correlated with the Ang II contractile response (P < 0.01). Administration of L-NAME also increased MAP values, and this effect was higher in those toads that presented a lower pressure response to Ang II (Pearson r = −0.68; P < 0.05). NO was present in all aortic rings, and its concentrations were negatively related to the Ang II contractile response (P < 0.036) and pressure response (Pearson r = −7.08; P < 0.001). These findings suggest that, in the B. arenarum toad, the NO system contra-regulates both the contractile and pressure Ang II responses, although its action could be different in each specimen.     

Effect of harvest time and physical form of alfalfa silage on chewing time and particle size distribution in boli,rumen content and faeces

The study examined the effects of physical form and harvest time of alfalfa silage on eating and ruminating activity and particle size distribution in feed boli, rumen content and faeces in dry cows. The alfalfa crop was harvested at two stages of growth (early: NDF 37%, late: NDF 44% in dry matter (DM)), and from each harvest, a chopped (theoretical cutting length: 19 mm) and an unchopped crop was ensiled in bales. The silages were fed restrictively to four rumen cannulated non-lactating Jersey cows (391 ± 26 kg) in a 4 × 4 Latin square design. The cows were fed restrictively 80% of their ad libitum intake twice daily. Chewing activity was recorded for 96 h continuously. Swallowed boli, rumen content, rumen fluid and faeces samples were collected, washed in nylon bags (0.01 mm pore size) and freeze-dried before dry sieving through 4.750, 2.360, 1.000, 0.500 and 0.212 mm pore sizes into six fractions. The length (PL) and width (PW) of particles within each fraction was measured by the use of image analysis. The eating activity (min/kg dry matter intake (P < 0.01) and min/kg NDF (P < 0.05)) was affected by harvest time. The mean ruminating time (min/kg DM) was affected by harvest time (P < 0.01), physical form (P < 0.05) and NDF intake per kg BW (P < 0.01). The proportion of washed particle DM of total DM in boli, rumen content, rumen fluid and faeces was affected by harvest time (P < 0.01) and highest by feeding late-harvested alfalfa silage. Two peaks on the probability density distribution function (PDF) of PW and PL values of boli, rumen content and faeces were identified. Chopping of the silage decreased the mean PL and PW, the most frequent PL (mode) and 95% percentile PL and PW values in boli. In the rumen content, chopping increased the mean PW (P < 0.05). The dimension sizes of faeces particles were not significantly affected by chopping. The mode PW value was lower in rumen content and faeces than in boli (P < 0.001), and the mode PL value was higher in boli and lower in faeces compared with rumen contents (P < 0.001). In conclusion, the mean total chewing activity per kg NDF decreased due to chopping and early harvest time. The mean PL and PW in boli decreased due to chopping and late harvest. The two peak values on the PDF (PL) and PDF (PW) of boli, rumen content and faeces particles are most likely related to the leaf and the stem residues.     

Influence of confounding factors on plasma Mid-Regional pro-Adrenomedullin and Mid-Regional pro-A-type Natriuretic Peptide concentrations in healthy individuals

Background: MRproADM and MRproANP can be used as diagnostic and prognostic markers in heart failure.

Aim: The objective was to identify confounding factors for the interpretation of plasma MRproADM and MRproANP concentrations.

Methods: A total of 518 healthy volunteers with a mean age of 60.84?±?7.41 years were analyzed. We evaluated the influence of demographic factors, renal function and echocardiographic indices on the candidate peptides.

Results: Multivariate analysis revealed that age (P?<?0.001), BMI (P?<?0.001) and eGFR (P?<?0.001) were independent predictors for MRproADM concentrations in healthy subjects. The independent predictors for MRproANP were age (P?<?0.001), female gender (P?<?0.001), heart rate (P?<?0.001) and eGFR (P?=?0.039).

Conclusion: The interpretation of both peptides is multifaceted due to confounders. Knowledge of these factors will further our understanding of how these peptides behave in health and in disease.     

Female protection in progressive renal disease is associated with estradiol attenuation of superoxide production

Background: Several types of renal disease progress at a faster rate in men compared with women, but the reasons for this sex difference are not well understood. Chronic renal disease is associated with elevated levels of toxic reactive oxygen species (ROS). Superoxide, the major ROS in the kidney, is generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.Objective: To determine if female protection from renal disease progression is consistent with 17β-estradiol (E₂) attenuation of superoxide production, this study was conducted to assess superoxide production in the renal cortex of male and female control and renal wrap (RW) rats, as well as in ovariectomized rats treated with vehicle or E₂.Methods: Sprague-Dawley rats were divided into 2 sham operation male (Sham-M) and female (Sham-F) control groups, and 4 RW hypertensive groups: RW-M; RW-F; RW ovariectomized females treated with vehicle (RW-OVX); and RW ovariectomized females treated with E₂, supplied as a 0.24 mg/60-day release pellet (RW-OVX+E₂). All groups were maintained on a high-sodium (4% NaCl) diet for 6 weeks.Results: Mean (SEM) markers of renal injury and oxidative stress, including urinary protein (mg/24 h: RW-M, 298 [31] vs RW-F, 169 [22]; P < 0.001), microalbuminuria (RW/Sham arbitrary units [AU]/24 h: M, 8.78 [0.58] vs F, 4.31 [1.0]; P < 0.005), and malondialdehyde (nmol/24 h: RW-M, 167 [23] vs RW-F, 117 [8.5]; P < 0.05) levels, as well as mean glomerular volume (μm³ × 10⁶: RW-M, 2.25 [0.16] vs RW-F, 1.25 [0.04]; P < 0.001) and the glomerulosclerotic index (AU: RW-M, 2.64 [0.19] vs RW-F, 1.10 [0.09]; P < 0.001) were greater in both control and RW males compared with females in the same treatment groups. Though RW surgery increased mean arterial pressure in both male and female rats, no sex difference was observed. Under these conditions, mean (SEM) renal cortical NADPH oxidase activity was 1.3-fold higher in RW males compared with RW females (relative light units [RLU]/180 sec: RW-M, 4080 [240] vs RW-F, 3200 [260]; P < 0.05). Ovariectomy increased NADPH oxidase activity by 1.4-fold (RLU/180 sec: RW-OVX, 4520 [184]; P < 0.01) under conditions in which the mean glomerular volume and glomerulosclerotic index were both increased by 1.5-fold, whereas E₂ replacement (RLU/180 sec: RW-OVX+E₂, 2745 [440]) prevented these effects. Furthermore, the effects on NADPH oxidase activity were mirrored by changes in the protein abundance of NADPH oxidase subunit p22P^phox.Conclusion: These results suggest that E₂ protects the female kidney in part by attenuating injury-induced increases in renal superoxide production.     

Reproducibility of Dual-Energy X-ray Absorptiometry Measurements in Prepubertal Girls

Objective : Regulation of growth and development, clinical assessment, and obesity are among the areas of nutritionrelated research, wherein accurate assessment of body composition is important. We want to test the hypothesis that dual-energy X-ray absorptiometry (DXA) measurements are reproducible in healthy girls. Research Methods and Procedures : We determined total body composition measurements in healthy prepubertal girls using DXA twice, 6 weeks apart. Results : We studied 61 healthy, normal-weight, prepubertal girls, aged 4.8 years to 10.3 years. The girls' DXA-derived mean weight between visits 1 and 2 significantly increased (27.14 kg vs. 27.80 kg, P<0.0001). The increased weight was due to significant increases in total body fat-free mass (FFM) (19.53 kg vs. 19.89 kg,P<O.001), total body bone mass (1.05 kg vs. 1.07 kg, P<0.0001), and total body fat mass (7.61 kg vs. 7.91 kg,P<0.03). The girls' DXA-derived mean total trunk mass between visits 1 and 2 significantly increased (11.23 kg vs. 11.63 kg, p<<0.0001), as did total leg mass (9.33 kg vs. 9.53 kg, p<<0.001), although no significant differences were observed in total arm mass (2.52 kg vs. 2.54 kg, p< = 0.37). The Pearson coefficient of correlation (r) and total coefficient of variation (CV) for intraindividual measurements by DXA were: weight—r = 0.99, CV= 1.97%; total body FFM—r = 0.96, CV = 2.30%; total body bone mass—r = 0.99, CV = 2.08%; total body fat mass—r = 0.96, CV = 6.55%; percentage total body fat— r = 0.91, CV = 5.69%; total trunk mass—r = 0.96, CV = 3.59%; total arm mass—r = 0.95, CV = 4.09%; and total leg mass—r = 0.99, CV = 2.75%. Discussion : Total body FFM, total body bone mass, total body fat mass, percentage of total body fat mass, as well as regional mass determinations by DXA, were highly reproducible in healthy, normal-weight, prepubertal girls. We highly recommend the use of DXA for total body composition studies in girls aged 5 years to 10 years.     

Consumption of a high-salt diet by ewes during pregnancy alters nephrogenesis in 5-month-old offspring

Maternal nutrition during pregnancy can affect kidney development in the foetus, which may lead to adverse consequences in the mature kidney. It was expected that high-salt intake by pregnant ewes would lead to a reduction in foetal glomerular number but that the ovine kidney would adapt to maintain homoeostasis, in part by increasing the size of each glomerulus. Merino ewes that were fed either a control (1.5% NaCl) or high-salt (10.5% NaCl) diet during pregnancy, as well as their 5-month-old offspring, were subjected to a dietary salt challenge, and glomerular number and size and sodium excretion were measured. The high-salt offspring had 20% fewer glomeruli compared with the control offspring (P < 0.001), but they also had larger glomerular radii compared with the control offspring (P < 0.001). Consequently, the cross-sectional area of glomeruli was 18% larger in the high-salt offspring than in the control offspring (P < 0.05). There was no difference in the daily urinary sodium excretion between the two offspring groups (P > 0.05), although the high-salt offspring produced urine with a higher concentration of sodium. Our results demonstrated that maternal high-salt intake during pregnancy affected foetal nephrogenesis, altering glomerular number at birth. However, the ability to concentrate and excrete salt was not compromised, which indicates that the kidney was able to adapt to the reduction in the number of glomeruli.     

Femoral to cerebral arterial blood flow redistribution and femoral vein distension during orthostatic tests after 4 days in the head-down tilt position or confinement

The first objective of this study was to confirm that 4 days of head-down tilt (HDT) were sufficient to induce orthostatic intolerance, and to check if 4 days of physical confinement may also induce orthostatic intolerance. Evidence of orthostatic intolerance during tilt-up tests was obtained from blood pressure and clinical criteria. The second objective was to quantify the arterial and venous changes associated with orthostatic intolerance and to check whether abnormal responses to the tilt test and lower body negative pressure (LBNP) may occur in the absence of blood pressure or clinical signs of orthostatic intolerance. The cerebral and lower limb arterial blood flow and vascular resistance, the flow redistribution between these two areas, and the femoral vein distension were assessed during tilt-up and LBNP by ultrasound. Eight subjects were given 4 days of HDT and, 1 month later, 4 days of physical confinement. Tilt and LBNP test were performed pre- and post-HDT and confinement. Orthostatic intolerance was significantly more frequent after HDT (63%) than after confinement (25%, P<0.001). Cerebral haemodynamic responses to tilt-up and LBNP tests were similar pre- and post-HDT or confinement. Conversely, during both tilt and LBNP tests the femoral vascular resistances increased less (P<0.002), and the femoral blood flow reduced less (P<0.001) after HDT than before HDT or after confinement. The cerebral to femoral blood flow ratio increased less after HDT than before (P<0.002) but remained unchanged before and after confinement. This ratio was significantly more disturbed in the subjects who did not complete the tilt test. The femoral superficial vein was more distended during post-HDT LBNP than pre-HDT or after confinement (P<0.01). In conclusion, 4 days of HDT were enough to alter the lower limb arterial vasoconstriction and venous distensibility during tilt-up and LBNP, which reduced the flow redistribution in favour of the brain in all HDT subjects. Confinement did not alter significantly the haemodynamic responses to orthostatic tests. The cerebral to femoral blood flow ratio measured during LBNP was the best predictor of orthostatic intolerance. Accepted: 12 December 1997     

Five-Year Change in Intraocular Pressure Associated with Changes in Arterial Blood Pressure and Body Mass Index. The Beijing Eye Study

Purpose

To examine a potential association between longitudinal changes in intraocular pressure (IOP), arterial blood pressure and body mass index (BMI) in a population-based setting.

Methods

The longitudinal population-based Beijing Eye Study included 2355 subjects with an age of 45+ years who were examined in 2006 and in 2011. The participants underwent a detailed ophthalmic examination including tonometry and measurement of arterial blood pressure and BMI.

Results

Data on IOP, arterial blood pressure and BMI measured in 2006 and in 2011 were available for 2257 (95.8%) subjects with a mean age of 59.5±9.7 years. The mean change in IOP was −1.25±2.26 mm Hg, mean change in mean blood pressure −7.4±12.1 mmHg, and mean change in BMI was 0.01±2.04 kg/m². In multivariate analysis, the 5-year change in IOP was significantly associated with a higher change in mean blood pressure (P<0.001; standardized regression coefficient Beta:0.11; regression coefficient B:0.02; 95% confidence interval (CI):0.01,0.03) after adjusting for younger age (P<0.001;Beta:−0.18;B:−0.04;95% CI:−0.05,−0.03), shorter body stature (P = 0.002;Beta:−0.06;B:−0.06;95% CI:−0.03,−0.01), thicker central corneal thickness (P<0.001;Beta:0.19;B:0.02;95% CI:0.01,0.02), deeper anterior chamber depth (P = 0.01;Beta:0.05;B:0.33;95% CI:0.07,0.60), and lower intraocular pressure at baseline (P<0.001;Beta:−0.56;B:−0.42;95% CI:−0.45,−0.39). If the analysis included only longitudinal parameters, the change in IOP was significantly associated with a higher change in mean arterial blood pressure (P<0.001;Beta:0.10;B:0.02;95% CI:0.01,0.03) and a higher change in body mass index (P<0.04;Beta:0.04;B:0.04;95% CI:0.01,0.09).

Conclusions

In the 5-year follow-up of our population-based sample, a change in IOP was associated with a corresponding change in arterial blood pressure and with a corresponding change in body mass index. These longitudinal data support the notion of a physiological relationship between arterial blood pressure, intraocular pressure and body mass index. These findings may be of interest for the discussion of the pathogenesis of glaucomatous optic neuropathy.     

Effects of posture, hypotension and locally applied vasoconstriction on the middle ear microcirculation in anaesthetized humans

Studies by laser-Doppler flowmetry of middle ear microcirculation changes induced by physical and chemical stimuli in the animal have only recently been made. This prospective study, performed in humans, was designed to compare the effects of a postural manoeuvre (headup tilt 30°), hypotension and locally applied vasoconstriction on middle ear blood flow during anaesthesia. Circulatory changes provoked by a headup tilt of 30°, and successive intravenous boluses of potent vasodilators, were compared with circulatory changes provoked by locally applied adrenaline, in ten healthy patients in good physical states undergoing middle ear surgical repair. Heart rate and direct arterial pressure were continuously recorded via a radial artery cannula. Middle ear blood flow was continuously recorded via a laser-Doppler probe placed on the promontorium cavi tympani. Metabolic parameters (partial pressure of O₂ and CO₂ in arterial blood, pH, arterial lactate concentrations) and arterial concentrations of propofol were measured just before and just after the experiment. Headup tilt did not modify heart rate, mean arterial pressure or middle ear blood flow. Vasodilators (nicardipine, nitroprusside, nitroglycerin) provoked a fall in arterial pressure (P<0.0001,P<0.0001,P<0.019, respectively), but did not induce any significant variations in heart rate; variations occurred in middle ear blood flow (P>0.05, not significant) which were different according to patients and agents. Locally applied adrenaline provoked a fall in the middle ear blood flow (P<0.0012), with no effect on heart rate and arterial pressure. There were no significant changes in metabolic values, or propofol serum concentrations. The behaviour of the middle ear blood flow submitted to hypotension, posture, or to vasoconstriction could be related to counteracting regulatory responses and/or to direct vascular effects.     

The Association of Restrained Eating With Weight Change Over Time in a Community‐Based Sample of Twins

We investigated the association of restrained eating with BMI and weight gain while controlling for the influence of genes and shared environment. Participants were 1,587 twins enrolled in the University of Washington Twin Registry (UWTR). Restrained eating was assessed by the Herman and Polivy Restraint Scale. Height and weight were self‐reported on two occasions. Analyses used generalized estimating equations or multiple linear regression techniques. Restraint Scale scores were positively associated with both BMI (adjusted β = 0.39 kg/m²; 95% confidence interval (CI) = 0.34–0.44; P < 0.001) and weight gain (adjusted β = 0.33 pounds; 95% CI = 0.17–0.49; P < 0.001). High Restraint Scale scorers had an adjusted mean BMI of 27.9 kg/m² (95% CI = 27.4–28.4) as compared to intermediate (mean = 25.5 kg/m²; 95% CI = 25.2–25.8) and low scorers (mean = 23.0 kg/m²; 95% CI = 22.7–23.3). In within‐pair analyses among 598 same‐sex twin pairs, the adjusted association between Restraint Scale scores and BMI persisted even when genetic and shared environmental factors were controlled for (adjusted β = 0.18; 95% CI = 0.12–0.24; P < 0.001), as did the association with weight gain (adjusted β = 0.37; 95% CI = 0.13–0.61; P = 0.003). In stratified analyses, dizygotic (DZ) twins differed more in BMI for a given difference in the Restraint Scale score than monozygotic (MZ) twins, for whom genetics are 100% controlled (adjusted β = 0.32; 95% CI = 0.20–0.44 vs. adjusted β = 0.10; 95% CI = 0.04–0.16; P = 0.001 for test of interaction). These data demonstrate that observed relationships between BMI, weight gain, and restrained eating, as assessed by the Restraint Scale, have a strong environmental influence and are not solely due to shared genetic factors.     

Sex Differences in Renal Nitric Oxide Synthase,NAD(P)H Oxidase,and Blood Pressure in Obese Zucker Rats

Background: By increasing renal oxidative stress, obesity may alter the protective effect of female sex on blood pressure (BP).Objectives: The aim of this study was to determine whether female rats had altered expression and activity of renal nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] oxidase and nitric oxide synthase (NOS), enzymes important in superoxide and nitric oxide generation, respectively, and whether this relationship was altered in obesity.Methods: Male and female, lean and obese Zucker rats were fed progressively higher levels of NaCl over 54 days while BP was measured by radiotelemetry. Kidneys were harvested after euthanization.Results: A total of 32 (n = 8/body type/sex) Zucker rats were examined. On a high-salt diet (4% NaC1), male and obese rats had significantly higher mean arterial blood pressure relative to female and lean rats (mm Hg: lean male = 108, lean female = 99, obese male = 129, and obese female = 123) and reduced renal cortical NOS activity (determined by 2-way analysis of variance; P < 0.05 for sex and body type). Immunoblotting revealed that cortical endothelial NOS protein abundance was reduced in obese but not in male rats. Surprisingly, lean female rats had the highest outer medullary protein levels of several NADPH oxidase subunits, including gp91phox, p47phox, and p67phox (% of lean male: 207, 196, and 151, respectively; P < 0.01 for all). However, renal NADPH activity was not increased in lean females, but was significantly increased in obese rats of both sexes (P < 0.05).Conclusions: High-NaCl diet increased BP modestly in obese females, but not at all in lean females, suggesting some loss of protection with obesity in female rats. Reduced cortical NOS activity (both in male and obese rats) and/or increased NADPH oxidase activity (obese rats) may have contributed to increased salt sensitivity of BP.     

Immunohistochemical and ultrastructural changes in the renal cortex of cadmium-treated rats

The aim of this study was to determine the cadmium-induced immunohistochemical and morphological changes in the renal cortex of adult male rats exposed to high doses of cadmium for 30 d. Animals used as controls received a standard diet and water ad libitum. The animals used for this study received 15 ppm CdCl₂ in their drinking water for 1 mo. The mean arterial pressure (MAP), the mean blood Cd level, and the mean tissue Cd content were significantly higher when compared to controls (p < 0.01). Immunohistochemical studies demonstrated a weak labeling to type IV collagen and laminin, but a strong labeling to fibronectin in the renal cortex of the Cd-treated animals when compared to controls. The ultrastructural alterations found in Cd-treated rats were a diminution in the amount of filtration slits, increased fusion of foot processes in epithelial cells of the glomeruli, increase of lysosomal structures and pinocytic vesicles as well as large mitochondria in proximal tubule cells, and degenerated cells in distal tubules. Additionally, the glomerular basement membrane was slightly thickened. In conclusion, cadmium toxicity results in alterations in the renal extracellular matrix and tubular or glomerular cells, which could play an important role in renal dysfunction.     

The anabolic action of intermittent parathyroid hormone on cortical bone depends partly on its ability to induce nitric oxide‐mediated vasorelaxation in BALB/c mice

There is strong evidence that vasodilatory nitric oxide (NO) donors have anabolic effects on bone in humans. Parathyroid hormone (PTH), the only osteoanabolic drug currently approved, is also a vasodilator. We investigated whether the NO synthase inhibitor L‐NAME might alter the effect of PTH on bone by blocking its vasodilatory effect. BALB/c mice received 28 daily injections of PTH[1–34] (80 µg/kg/day) or L‐NAME (30 mg/kg/day), alone or in combination. Hindlimb blood perfusion was measured by laser Doppler imaging. Bone architecture, turnover and mechanical properties in the femur were analysed respectively by micro‐CT, histomorphometry and three‐point bending. PTH increased hindlimb blood flow by >30% within 10 min of injection (P < 0.001). Co‐treatment with L‐NAME blocked the action of PTH on blood flow, whereas L‐NAME alone had no effect. PTH treatment increased femoral cortical bone volume and formation rate by 20% and 110%, respectively (P < 0.001). PTH had no effect on trabecular bone volume in the femoral metaphysis although trabecular thickness and number were increased and decreased by 25%, respectively. Co‐treatment with L‐NAME restricted the PTH‐stimulated increase in cortical bone formation but had no clear‐cut effects in trabecular bone. Co‐treatment with L‐NAME did not affect the mechanical strength in femurs induced by iPTH. These results suggest that NO‐mediated vasorelaxation plays partly a role in the anabolic action of PTH on cortical bone. © 2016 The Authors. Cell Biochemistry and Function published by John Wiley & Sons, Ltd.     

Immediate physiological responses of healthy volunteers to different types of music: cardiovascular, hormonal and mental changes

A group of 20 healthy volunteers [10 women, 10 men; median age 25 (20–33) years] were examined by means of pulsed wave Doppler echocardiography, blood sample analysis and psychological testing before and after listening to three different examples of music: a waltz by J. Strauss, a modern classic by H. W. Henze, and meditative music by R. Shankar. To assess small haemodynamic changes, mitral flow, which reflects left ventricular diastolic behaviour, was measured by Doppler ultrasound. Heart rate, arterial blood pressure and plasma concentrations of adrenocorticotropic hormone, cortisol, prolactin, adrenaline, noradrenaline, atrial natriuretic peptide (ANP) and tissue plasminogen activator (t-PA) were determined simultaneously. Transmitral flow profile is characterized by early E-wave and late atrial induced A-wave. Velocity-time integrals were measured and the atrial filling fraction was calculated. The mental state was measured by using a psychological score (Zerssen) with low values (minimum 0) for enthusiastic and high values (maximum 56) for depressive patterns. Music by J. Strauss resulted in an increase of atrial filling fraction (AFF; 29% vs 26%;P<0.05) and ANP (63 pg·ml^–1 vs 60 pg·ml^–1;P<0.05). The mental state was improved (Zerssen: 6.5 vs 11 points;P<0.05). After the music of H. W. Henze prolactin values were lowered (7.7 ng·ml^–1 vs 9.1 ng·ml^–1;P<0.01). The music of R. Shankar led to a decrease of cortisol concentrations (57 ng·ml^–1 vs 65 ng·ml^–1;P<0.001), noradrenaline concentrations (209 g·l^–1 vs 256 g·l^–1;P<0.01) andt-PAantigen concentrations (1.1 ng·ml^–1 vs 1.4 ng·ml^–1;P<0.05). Heart rate and blood pressure remained unchanged during the whole experiment. We concluded that different types of music induced changes of left ventricular diastolic function and plasma hormone concentrations. After rhythmic music (Strauss) AFF and ANP increased significantly, the mental state being improved. Meditative music (Shankar) lowered plasma cortisol, noradrenaline and t-PA concentrations; the observed increase of early left ventricular filling was not statistically significant. Prolactin concentrations decreased after modern music (Henze). Thus, it would seem to be possible to detect cardiovascular changes following different types of music by Doppler ultrasound and hormone analysis, meditative music having promising therapeutic implications in the treatment of conditions of stress.This paper contains data from J. Vollert's work for his doctoral degree.     

Blood flow in the carotid artery during breath-holding in relation to diving bradycardia

The present study investigated the mechanism of diving bradycardia. A group of 14 healthy untrained male subjects were examined during breath-holding either out of the water (30–33°C), in head-out immersion, or in whole-body submersion (27–29°C) in a diving pool. Blood velocity, blood volume flow in the carotid artery, diastolic blood pressure and electrocardiogram were measured and recorded during the experiments. The peak blood velocity increased by 13.6% (P < 0.01) and R-wave amplitude increased by 57.1% (P < 0.005) when the subjects entered water from air. End-diastolic blood velocity in the carotid artery increased significantly during breath-holding, e.g. increased from 0.20 (SD 0.02) m · s⁻¹ at rest to 0.33 (SD 0.04) m · s⁻¹ (P < 0.001) at 50.0 s in breath-hold submersion to a 2.0-m depth. Blood volume flow in the carotid artery increased by 26.6% (P < 0.05) at 30 s and 36.6% (P < 0.001) at 40 s in breath-hold submersion to a 2.0-m depth. Diastolic blood pressure increased by 15.4% (P < 0.01) at 60 s during breath-holding in head-out immersion. Blood volume flow, and diastolic blood pressure increased significantly more and faster during breath-holding in submersion than out of the water. There was a good negative correlation with the heart rate: the root mean square correlation coefficient r was 0.73 (P < 0.001). It was concluded that an increased accumulation of blood in the aorta and arteries at end-diastole and decreased venous return, caused by an increase in systemic peripheral resistance during breath-holding, underlies diving bradycardia. Accepted: 22 November 1996