Changes in regional brain synaptosomal high affinity choline uptake during the development of hypertension in spontaneously hypertensive rats

The high-affinity uptake of choline (HAChU) by freshly prepared crude synaptosomal fractions was employed as relative measure of regional brain cholinergic activity. TheV _max for uptake as determined by the accumulation of a tracer amount of³H-choline in the presence of unlabeled choline (0.2–2 M) varied 6 fold depending upon the region examined (striatum>hypothalamus>medulla-pons). HAChU was hemicholinium-3-sensitive and linear at 37°C from 1 to 8 min in all brain regions. Respective brain synaptosomal fractions derived from adult (12 week old) spontaneously hypertensive (SH) rats and normotensive Wistar Kyoto (WK) rats revealed no difference in theV _max for HAChU from synaptosomes derived from the striatum of either strain. However, there was a significant increase in theV _max for HAChU measured from the medulla-pons of SH rats compared with WK rats. In older (22 weeks) rats, theV _max for HAChU was 78% greater than age-matched WK control rats. In addition, a highly significant correlation was found between resting systolic blood pressure and theV _max for HAChU both in the medulla-pons (r=0.76) and hypothalamus (r=0.48). That the increase in HAChU in SH rats was not a consequence of elevated pressure, was indicated by the lack of effect of prolonged i.v. infusion of pressor agents in normotensive rats on HAChU. These findings are consistent with a role for brain cholinergic neurons in the maintenance of hypertension in SH rats.     

Multinuclear NMR studies of intracellular cations in the prehypertensive rat kidney

We previously reported a significant derangement of intracellular free calcium ion concentration in the isolated perfused kidney of adult spontaneously hypertensive rat (SHR) (J. Biol. Chem. 267, 3637–3643, 1992). In order to investigate whether an abnormality in intracellular free calcium or another ion precedes the development of elevated blood pressure in SHR, we have now compared intracellular free Ca²⁺, Na⁺ and pH, using ³¹P, ¹⁹F, and triple quantum-filtered (TQ) ²³Na NMR, in perfused kidneys from prehypertensive young SHR and normotensive young Wistar-Kyoto (WKY) rats (5–6 weeks old) which showed no significant difference in blood pressure B.P.=120±5 mmHg and 115±3 mmHg, for SHR and WKY rats, respectively). Like the adult kidney, no significant differences in intracellular ATP concentration or intracellular pH were found between young prehypertensive SHR and normotensive WKY rat kidneys. The TQ ²³Na NMR signal was 47% higher in the SHR kidney, but, due to biological variability and measurement errors, this difference could not be shown to be statistically significant. However, a significant (40%; P<0.05) increase was found in O₂ consumption rate, a measure of the Na⁺/K⁺-ATPase activity, of the young prehypertensive SHR kidney in comparison to the age-matched WKY rat kidney (7.25±0.75 for SHR vs. 5.17±0.18 μmola O₂/min g for WKY rat, n = 6). Furthermore, a highly significant (92%; P<0.02) increase in intracellular free Ca²⁺ concentration was observed in kidneys from young SHR that had noy yet been developed high blood pressure in comparison to the kidneys from young normotensive WKY rats (648±76 nM vs. 339±39 nM, n = 4, despite the fact that there was no significant difference in blood pressure. Increased intracellular free Ca²⁺ thus appears to be part of a primary defect, in the prehypertesive young SHR kidney, which may, by way of increased release of arachidonic acid, and subsequent increased production of vasoconstricting arachidonic acid metabolites via the cytochrome P450 pathway, induce elevated blood pressure in the adult SHR.     

Exercise prevents leptin-induced increase in blood pressure in Sprague–Dawley rats

Although leptin has been shown to increase blood pressure (BP), it is however unclear if this increase can be prevented by exercise. This study therefore investigated the effect of leptin treatment with concurrent exercise on blood pressure (BP), sodium output, and endothelin-1 (ET-1) levels in normotensive rats. Male Sprague–Dawley rats weighing 250–270 g were divided into four groups consisting of a control group (n?=?6), leptin-treated (n?=?8), non-leptin-treated exercise group (n?=?8), and a leptin-treated exercise group (n?=?8). Leptin was given subcutaneously daily for 14 days (60 μg/kg/day). Animals were exercised on a treadmill for 30 min at a speed of 0.5 m/s and at 5° incline four times per week. Measurement of systolic blood pressure (SBP) and collection of urine samples for estimation of sodium and creatinine was done once a week. Serum samples were collected at the end of the experiment for determination of sodium, creatinine and ET-1. At day 14, mean SBP and serum ET-1 level in the leptin-treated group was significantly higher than that in the control group whereas mean SBP and serum ET-1 level was significantly lower in the leptin-treated exercise group than those in leptin-treated and control groups. Creatinine clearance, urinary sodium excretion, and urine output were not different between the four groups. Regular treadmill exercise prevents leptin-induced increases in SBP in rats, which might in part result from increased urinary sodium excretion and preventing the leptin-induced increases in serum ET-1 concentration.     

Abnormal functional development of sympathetic nerve terminal-smooth muscle complex in neonatal spontaneously hypertensive rats

In neonatal and young adult SH and WK rats, maturation of a functional unit consisting of sympathetic nerve terminals and smooth muscle (levator palpebrae) was assessed $\text{in vivo}$ by measuring the contractile response to tyramine, an agent which releases endogenous norepinephrine from sympathetic nerve terminals. Responses in SH are comparable to WK at 5–6 days postnatally, smaller from the 8th through 19th day and larger in young adults (41–46 days old). Results indicate that functional maturation of the nerve terminal-smooth muscle complex is retarded in SH relative to WK during the 2nd and 3rd postnatal weeks. It is suggested that retardation in the neonatal SH rat is an expression of a genetic defect in the growth of the complex and that the enhanced response in young adult SH is a consequence of the neonatal abnormality.     

Depressor effect of diabetes in the spontaneously hypertensive rat: associated changes in heart performance

Effects of streptozotocin-induced diabetes (8 weeks) on the performance of perfused hearts from spontaneously hypertensive (SH) rats were compared with effects on normotensive Wistar-Kyoto (WK) and Sprague-Dawley (SD) rat hearts. Diabetes markedly decreased systolic arterial pressure (SAP) of SH rats in vivo but did not affect SAP of either of the normotensive strains. Diabetes also reduced heart size of SH and normotensive rats and reversed absolute left ventricular hypertrophy (wall-to-lumen ratios and left-to-right ventricular weight ratios) of SH rats. Heart perfusion at the end of the 8-week period revealed that diabetes (i) reduced hydraulic work at high pressure loads and efficiency of contraction (work/mu LO2 consumed) of SH rat hearts but not of WK or SD hearts, and (ii) depressed left ventricular pulse pressure development (LVPP) and contractility (LV + dP/dt) of SH hearts more extensively than it reduced these variables in either of the normotensive control groups. Effects of diabetes which were similar in hypertensive and normotensive hearts were reductions in stroke work at high volume loads and depressions in LV-dP/dt. Attendant hypothyroidism probably contributed to the reductions in SAP, heart size, LVPP, LV+ and -dP/dt, and stroke work but not to the decreased efficiency or reversal of hypertrophy of SH rat hearts. Malnutrition of SH rats, like hypothyroidism, also decreased heart size without reversing hypertrophy but had no effect on SAP and only reduced LV-dP/dt. The results show that diabetes reversed hypertrophy and selectively reduced contraction efficiency, contractility, and LVPP of SH hearts, but otherwise the effects of diabetes in hypertensive and normotensive rat strains were similar to each other.(ABSTRACT TRUNCATED AT 250 WORDS)     

An immunohistochemical analysis of SERT in the blood–brain barrier of the male rat brain

5-Hydroxytryptamine (5-HT) was originally discovered as a vasoconstrictor. 5-HT lowers blood pressure when administered peripherally to both normotensive and hypertensive male rats. Because the serotonin transporter (SERT) can function bidirectionally, we must consider whether 5-HT can be transported from the bloodstream to the central nervous system (CNS) in facilitating the fall in blood pressure. The blood–brain barrier (BBB) is a highly selective barrier that restricts movement of substances from the bloodstream to the CNS and vice versa, but the rat BBB has not been investigated in terms of SERT expression. This requires us to determine whether the BBB of the rat, the species in which we first observed a fall in blood pressure to infused 5-HT, expresses SERT. We hypothesized that SERT is present in the BBB of the male rat. To test this hypothesis, over 500 blood vessels were sampled from coronal slices of six male rat brains. Immunofluorescence of these coronal slices was used to determine whether SERT and RecA-1 (an endothelial cell marker) colocalized to the BBB. Blood vessels were considered to be capillaries if they were between 1.5 and 23 µm (intraluminal diameter). SERT was identified in the largest pial vessels of the BBB (mean ± SEM = 228.70 ± 18.71 µm, N = 9) and the smallest capillaries (mean ± SEM = 2.75 ± 0.12 µm, N = 369). SERT was not identified in the endothelium of blood vessels ranging from 20 to 135 µm (N = 45). The expression of SERT in the rat BBB means that 5-HT entry into the CNS must be considered a potential mechanism when investigating 5-HT-induced fall in blood pressure.     

The Effect of Repeated Episodes of Dietary Restriction and Refeeding on Systolic Blood Pressure and Food Intake in Exercise‐Trained Normotensive Rats

Objective: To explore the effects of weight cycling and exercise on blood pressure and macronutrient intake in Sprague‐Dawley rats. Research Methods and Procedures: Female Sprague‐Dawley rats (n = 62; 5 months old) were assigned to an ad libitum (Con) or weight‐cycled (Cyc) group. They were either sedentary (Con‐Sed and Cyc‐Sed) or exercise‐trained (Con‐Ex and Cyc‐Ex) on a motorized treadmill (20 m/minute; 60 minutes/day; 6 days/week). The Cyc groups underwent 2 cycles of 3 weeks of 60% food restriction followed by 5 weeks of ad libitum refeeding using a macronutrient self‐selection diet. Body mass and food intake were analyzed weekly. Systolic blood pressure (SBP) was measured at baseline and during the first and fifth weeks of each refeeding. Results: For both cycling periods, SBP was elevated in Cyc vs. Con groups at Week 1 of refeeding, but was similar among groups by Week 5 of refeeding. Both Con groups had greater total energy intake than the Cyc groups for both cycling periods (Cycle 1: 2882.2 ± 75.1, Con‐Sed; 2916.1 ± 67.1, Con‐Ex; 2692.2 ± 58.7, Cyc‐Sed; and 2780.5 ± 52.4 kcal, Cyc‐Ex) (Cycle 2: 2815.8 ± 75.1, Con‐Sed; 2938.8 ± 49.4, Con‐Ex; 2577.1 ± 60.5, Cyc‐Sed; and 2643.5 ± 65.9 kcal, Cyc‐Ex). Relative fat intake (percentage of total kcal/week) was significantly less for Con‐Ex and Cyc‐Ex than Con‐Sed and Cyc‐Sed throughout both refeeding periods. Discussion: Weight cycling failed to produce significant sustained effects on SBP, body mass, or food intake. Exercise training, irrespective of diet, lowered dietary fat intake.     

The Relationship Between Serum Calcium Level, Blood Lipids, and Blood Pressure in Hypertensive and Normotensive Subjects who Come from a Normal University in East of China

Previous studies revealed that low calcium intake is related to high prevalence of cardiovascular diseases such as hypertension. However, the relationship between serum calcium and blood pressure was unclear. The prevalence of hypertension is high in China. Thus, the aim of this study was to evaluate the serum calcium level between hypertensive and normotensive groups and to investigate the correlation between serum calcium, blood pressure, and blood lipid parameters. A total of 1,135 adult subjects participated in this study and were divide into two study groups: a hypertensive group (n?=?316) who had 140 mmHg or higher in systolic blood pressure (SBP) or 90 mmHg or higher in diastolic blood pressure (DBP) and an age- and sex-matched normotensive group (n?=?819, 120 mmHg or less SBP and 80 mmHg or less DBP). Our results indicate a significant trend for men (60 years old or older) in the direction of decreasing blood pressure with increasing serum calcium level, but no trend for women was indicated. In the normotensive group, a significant positive correlation was found between DBP and total cholesterol (P?<?0.01) and triglyceride (P?<?0.01), Likewise, triglyceride was positively correlated with SBP (P?<?0.01). Overall, these data suggest that serum calcium may have an influence in the blood pressure of older male subjects with hypertension and in blood lipid profiles of normotensive subjects.     

A comparison of two subarachnoid α2-agonists,xylazine and clonidine,with respect to duration of antinociception,and hemodynamic effects in goats

Subarachnoid administration of clonidine and xylazine produces antinociception in several species and in humans. The present study compares these two drugs administered by the subarachnoid route to goats. Goats (n=6) were randomly assigned to three treatment groups. All animals of each group received 0.06 mg kg⁻¹ clonidine (CLO), 0.1 mg kg⁻¹ xylazine (XIL) and 0.9% saline solution (SS), with a minimum interval of 1 week between treatments. All injections were made into the subarachnoid space between the last lumbar vertebra and the first sacral vertebra. Analgesia, ataxia, sedation, cardiovascular and respiratory effects, and rectal temperature were evaluated at predefined regular time intervals before drug administration (baseline) and after administration. The onset of analgesia by clonidine and xylazine was observed in 6.8±1.8 and 9.5±2.6 min (mean±S.D.), respectively. Both α₂-agonists produced analgesia of dorsocaudal rib areas, flanks, hind limbs, perineum and tail, sedation and ataxia. The duration of antinociception after clonidine administration was 118.8±24 min and after xylazine 88.3±15 min (mean±S.D.). Clonidine and xylazine subarachnoidally administered induced a significant (P<0.05) decrease in heart and respiratory rates and hypothermia in relation to the basal value. Neither drug significantly altered blood pressure. Both α₂-agonist drugs induced frequent diuresis and an increase in salivation. We conclude that subarachnoid clonidine produces longer antinociception with less ataxia than xylazine in goats. However, the drug induced bradycardia, a decrease in the respiratory rate and hypothermia, with a small compromise in the blood pressures at the doses studied. Further studies should be done to determine whether this analgesia is sufficient for surgical procedures.     

Dietary sodium regulation of blood pressure and renal alpha 1- and alpha 2-receptors in WKY and SH rats

We studied the effect of high (8%) versus normal (0.6%) sodium diet on renal α₁ and α₂-adrenergic receptors and on blood pressure in Okamoto-Aoki spontaneously hypertensive (SH) and Wistar Kyoto (WKY) “normotensive” rats. SH rats had higher renal α₁ (p<.05) and ga₂-receptor densities (p<.05) and blood pressure (p<.001) than WKY rats on normal salt diets. High salt (8% NaCl) diet increased the already elevated α₂-receptor density (p<.001) and blood pressure (p<.005) even higher in the SH rats after two and after five weeks. After two weeks of high salt diet α₂-receptor density had increased by 27% (p<.01) in WKY rats and the blood pressure had increased (p>.01). Ingestion of the high salt diet for 5 weeks increased blood pressure from 130 mmHg to 174 mmHg (p<.001) and α₂-receptor density from 255 and 375 fMo1/mg protein (p<.001) in the WKY rats. We conclude: 1) Renal α₁ and α₂-receptor density is higher in the SH than in WKY rats 2) The dietary sodium-induced increase in α₂-receptor density in WKY rats and anedates most of the elevation of blood pressure 3) The increase in blood pressure is directly related to the increase in renal α₂-receptor density in SH and WKY rats. Thus, the increment in renal α₂-receptor density appears to be a genetic marker of hypertension and could be related to a basic hypertensive mechanism.     

The antihypertensive action of arachidonic acid in the spontaneous hypertensive rat and its antagonism by anti-inflammatory agents

Changes in arterial blood pressure and heart rate were observed in the spontaneous hypertensive (SH) rat following the intravenous administration of arachidonic acid, the precursor of prostaglandin E₂ (PGE₂). The pronounced fall in blood pressure and the increase in heart rate induced by arachidonic acid were also observed in SH rats receiving either prostaglandin E₁ (PGE₁) or PGE₂. In SH rats receiving various anti-inflammatory agents the cardiovascular responses to arachidonic acid were inhibited, but the blood pressure responses to the E-type prostaglandins were not altered. The data are interpreted to suggest that cardiovascular changes induced by arachidonic acid are mediated via its conversion to PGE₂.     

The decreased expression of Stat3 and p-Stat3 in preeclampsia-like rat placenta

This study aims to investigate the expression of Stat3 and p-Stat3 in the placenta of a preeclampsia-like rat model induced by Nωnitro-l-arginine methyl ester (l-NAME). Two-to three-month-old (20 males, 40 females) Sprague–Dawley rats were used in this study. After conception was confirmed by vaginal smears, on the thirteenth day of pregnancy, the animals were allocated into two groups: control (0.9% NaCl administered) group and l-NAME (75 mg/kg) group. After the treatment of l-NAME, there was a significant increase in systolic blood pressure (SBP) levels in the l-NAME group (148.5?±?5.71 mmHg) on day 21 compared to the SBPs in the control group (117.5?±?4.57 mmHg) (P?<?0.001). There was also an increase in total proteinuria on day 21 in the l-NAME group (766.57?±?17.7 mg/L), when compared to the control group (459.89?±?20.1 mg/L) (P?<?0.001). Moreover, we also found a decrease in fetal numbers and fetal weight in the PE group in comparison to the control group. After the rats were sacrificed, the placentas were obtained from both groups. We found that the l-NAME group exhibited fewer placentas compared with the control group. Furthermore, the immunohistochemistry (IHC) and Western blot results showed that decreased expression of Stat3 and p-Stat3 were detected in the placenta of the preeclampsia-like rat model compared to Stat3 and p-Stat3 in the control group. We found the expression and activation of Stat3 and p-Stat3 were decreased in the placenta of the l-NAME-induced preeclampsia rat model.     

Visit-to-visit blood pressure variability and the risk of stroke in the Netherlands: A population-based cohort study

BackgroundApart from blood pressure level itself, variation in blood pressure has been implicated in the development of stroke in subgroups at high cardiovascular risk. We determined the association between visit-to-visit blood pressure variability and stroke risk in the general population, taking into account the size and direction of variation and several time intervals prior to stroke diagnosis.Methods and findingsFrom 1990 to 2016, we included 9,958 stroke-free participants of the population-based Rotterdam Study in the Netherlands. This is a prospective cohort study including participants aged 45 years and older. Systolic blood pressure (SBP) variability was calculated as absolute SBP difference divided by mean SBP over 2 sequential visits (median 4.6 years apart). Directional SBP variability was defined as SBP difference over 2 visits divided by mean SBP. Using time-varying Cox proportional hazards models adjusted for age, sex, mean SBP, and cardiovascular risk factors, hazard ratios (HRs) for stroke up to January 2016 were estimated per SD increase and in tertiles of variability. We also conducted analyses with 3-, 6-, and 9-year intervals between variability measurement and stroke assessment. These analyses were repeated for diastolic blood pressure (DBP). The mean age of the study population was 67.4 ± 8.2 years and 5,776 (58.0%) were women. During a median follow-up of 10.1 years, 971 (9.8%) participants had a stroke, including 641 ischemic, 89 hemorrhagic, and 241 unspecified strokes. SBP variability was associated with an increased risk of hemorrhagic stroke (HR per SD 1.27, 95% CI 1.05–1.54, p = 0.02) and unspecified stroke (HR per SD 1.21, 95% CI 1.09–1.34, p < 0.001). The associations were stronger for all stroke subtypes with longer time intervals; the HR for any stroke was 1.29 (95% CI 1.21–1.36, p < 0.001) at 3 years, 1.47 (95% CI 1.35–1.59, p < 0.001) at 6 years, and 1.38 (95%CI 1.24–1.51, p < 0.001) at 9 years. For DBP variability, we found an association with unspecified stroke risk. Both the rise and fall of SBP and the fall of DBP were associated with an increased risk for unspecified stroke. Limitations of the study include that, due to an average interval of 4 years between visits, our findings may not be generalizable to blood pressure variability over shorter periods.ConclusionsIn this population-based study, we found that visit-to-visit blood pressure variation was associated with an increased risk of unspecified and hemorrhagic stroke, independent of direction of variation or mean blood pressure.

In a population-based cohort study, Alis Heshmatollah and colleagues investigate the associations between blood pressure variability and risk of stroke among adults in the Netherlands.     

Proteomic profiling of human bone marrow mesenchymal stem cells under shear stress

Diets containing 8% salt or 4% fructose (FR) cause insulin resistance and increase tissue methylglyoxal and advanced glycation end products (AGEs), platelet cytosolic-free calcium, and systolic blood pressure (SBP) in rats. In WKY rats, we have shown that moderately high salt, 4% NaCl (MHS) alone in diet does not cause hypertension, and when given along with 4% FR it does not have an additive effect. N-acetylcysteine (NAC) or l-arginine (ARG), treatment alone does not prevent hypertension in this model. The objectives of this study were to investigate the effect of NAC plus ARG in diet on SBP, platelet cytosolic-free calcium in a MHS + FR model, and to measure the plasma levels of methylglyoxal and the AGE, methylglyoxal-derived hydroimidazolone (MGH). At 7 weeks of age, WKY rats were divided into three groups: control group was given regular rat chow (0.7% NaCl) and water; MHS + FR group, diet containing 4% NaCl and 4% FR in drinking water; and MHS + FR + NAC + ARG group, MHS diet supplemented with 1.5% N-acetylcysteine (NAC) and 1.5% l-arginine (ARG), and 4% FR in drinking water, and followed for 6 weeks. NAC + ARG prevented the increase in platelet cytosolic-free calcium and SBP in MHS + FR treated rats. There was no difference in mean values of plasma methylglyoxal and MGH among the groups. In conclusion, NAC + ARG treatment is effective in preventing hypertension in a moderately high salt + FR-induced animal model. Plasma methylglyoxal and MGH may not represent tissue modification or, alternatively, other tissue AGEs, derived from methylglyoxal or other aldehydes, may be involved in hypertension in this model.     

The effect of age on beta-adrenergic receptors and adenylate cyclase activity in rat erythrocytes.

Beta-adrenergic receptors and catecholamine-sensitive adenylate cyclase activity were studied in erythrocytes obtained from rats 6 weeks, 6 months, and 15 months of age. Intact erythrocytes from 6 week old rats contained significantly more beta receptors (411 ± 31 sites/cell) than 6 month (328 ± 21) or 15 month old rats (335 ± 16), as determined by binding of [¹²⁵I] iodohydroxybenzylpindolol. Erythrocytes from 6 week old rats also contained significantly greater isoproterenol-sensitive adenylate cyclase activity (95.0 ± 9.4pmoles/10⁹ cells) than erythrocytes from 6 month (27.9 ± 3.3) or 15 month old rats (23.7 ± 3.6). The erythrocyte population of 6 week old rats was bigger (mean corpuscular volume = 62 ± 2μ^3/cell) than the older rat erythrocytes (47 ± 1μ³ and 48 ± 1μ³). When the data were expressed relative to a unit of cell volume, there was no difference in the density of beta receptors among all three populations but a progressive and significant fall in hormone-sensitive adenylate cyclase activity. In the rat erythrocyte, the age-related loss of adenylate cyclase activity is not accompanied by changes in β-receptor density.     

Nordic Walking Improves Cardiometabolic Parameters,Fitness Performance,and Quality of Life in Older Adults With Type 2 Diabetes

ObjectiveTo assess the effect of Nordic walking (NW) on cardiometabolic health, physical performance, and well-being in sedentary older adults with type 2 diabetes (T2D).MethodsFifteen subjects with T2D (female, 5; male, 10; age, 65 ± 6.2 years [mean ± standard deviation]; body mass index, 27.3 ± 4.9 kg/m² [mean ± standard deviation]) were enrolled in a 6-month NW training program. The fasting glucose and glycosylated hemoglobin levels, lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), systolic blood pressure (SBP), and diastolic blood pressures were measured before and after the intervention. Participants’ quality of life (Short-Form Health Survey) and physical fitness (6-minute walking test) were also evaluated.ResultsCompared with baseline, NW significantly improved the fasting glucose level (103.5 ± 18.5 vs 168.7 ± 37.7 mg/dL, P = .01), SBP (121.8 ± 12.2 vs 133 ± 14.4 mm Hg, P = .02), physical fitness (759.88 ± 69 vs 615.5 ± 62.6 m, P < .001), and both mental health (54.5 ± 4.4 vs 45.7 ± 5.6, P < .01) and physical health (49.8 ± 4.7 vs 40.3 ± 5.9, P < .01). The levels of glycosylated hemoglobin (6.15% ± 0.8% vs 6.4% ± 1%, P = .46), total cholesterol (162.2 ± 31.2 vs 175.5 ± 28.8 mg/dL, P = .13), low-density lipoprotein cholesterol (95.2 ± 24.2 vs 106.3 ± 32.3 mg/dL, P = .43), and triglycerides (135.5 ± 60.8 vs 127.6 ± 57.4 mg/dL, P = 0.26) improved without reaching significance.ConclusionNW training improved the glycemic levels, SBP, physical fitness, and perception of quality of life in older adults with T2D. NW represents a suitable complementary strategy to improve the global health status in this population.     

A geometry-based model for non-invasive estimation of pressure gradients over iliac artery stenoses

The aim of this study was to develop and verify a model that provides an accurate estimation of the trans-lesion hyperemic pressure gradient in iliac artery stenoses in seconds by only using patient-specific geometric properties obtained from 3-dimensional rotational angiography (3DRA).Twenty-one patients with symptomatic peripheral arterial disease (PAD), iliac artery stenoses and an ultrasound based peak systolic velocity ratio between 2.5 and 5.0 underwent 3DRA and intra-arterial pressure measurements under hyperemic conditions. For each lesion, geometric properties were extracted from the 3DRA images using quantitative vascular analysis software. Hyperemic blood flow was estimated based on stenosis geometry using an empirical relation. The geometrical properties and hyperemic flow were used to estimate the pressure gradient by means of the geometry-based model. The predicted pressure gradients were compared with in vivo measured intra-arterial pressure measurements performed under hyperemic conditions.The developed geometry-based model showed good agreement with the measured hyperemic pressure gradients resulting in a concordance correlation coefficient of 0.86. The mean bias ± 2SD between the geometry-based model and in vivo measurements was comparable to results found by evaluating the actual computational fluid dynamics model (−1.0 ± 14.7 mmHg vs −0.9 ± 12.7 mmHg).The developed model estimates the trans-lesional pressure gradient in seconds without the need for an additional computational fluid dynamics software package. The results justify further study to assess the potential use of a geometry-based model approach to estimate pressure gradient on non-invasive CTA or MRA, thereby reducing the need for diagnostic angiography in patients suffering from PAD.     

Effects of Angiotensin II type I receptor shRNA on blood pressure and left ventricular remodeling in spontaneously hypertensive rats

This study was designed to investigate the effects of the Angiotensin II type I receptor (AT1R) shRNA on blood pressure and left ventricular remodeling in spontaneously hypertensive rats. Ten Wistar Kyoto (WKY) rats were used as a normal blood pressure control group, and 20 spontaneously hypertensive rats (SHR) were randomly divided into the experimental and hypertension control groups. The rats in the experimental group were injected with AT1R shRNA recombinant adenovirus (Ad5-AT1R-shRNA) via a tail vein, and the rats in the other two groups were injected with recombinant adenovirus (Ad5-EGFP). The systolic blood pressure (SBP) at rat arteria caudalis was measured before and after the injection, and the heart, kidney, aorta, and adrenal tissues were obtained two days after repeated injection to observe the distribution of Ad5-AT1R-shRNA under a fluorescence microscope. Before the injection of Ad5-AT1R-shRNA, the blood pressure of the experimental group and the hypertension control group was significantly higher than that of the normal blood pressure control group (P<0.01). After two injections, the blood pressure in the experimental group decreased significantly, and the duration of blood pressure reduction reached 19 days. In the experimental group, the kidney, heart, aorta, and adrenal gland tissues showed vigorous fluorescence expression under the fluorescence microscope. Repeated administration of Ad5-AT1R-shRNA has a long-lasting hypotensive effect on SHR and can significantly improve ventricular remodeling.     

Influence of dietary polyunsaturated fatty acids on renal & aortic prostaglandin synthesis in 1 kidney 1 clip goldblatt hypertensive rats

To study the influence of dietary modification on prostaglandin synthesis and on blood pressure regulation, the effects of dietary enrichment with linolenic or linoleic acid was compared with standard rat chow in 3 groups of 13 rats before and after renal artery constriction and contralateral nephrectomy. Before renal artery constriction 4 weeks supplementation with 40 en% linseed oil (53% linolenic acid) increased renal linolenic acid, decreased arachidonic acid, and suppressed synthesis of 6-keto-PGF_1α and PGE₂ by renal homogenates (33% and 38% respectively, p<0.01) compared with standard diet. Rats fed on 40 en % sunflower seed oil (63% linoleic acid) increased renal prostaglandin synthesis (p<0.05) compared with linseed oil, but not compared with standard diet. Seven weeks after renal artery constriction renal and aortic 6-keto-PGF_1α and PGE₂ were suppressed 30% to 50% (p<0.05) by linseed oil supplements compared with sunflower seed oil and standard diets. In the sunflower seed oil group aortic 6-keto-PGF_1α correlated (r = 0.75, p<0.02) with final systolic blood pressure. Final systolic blood pressures were similar in linseed oil (152.9 mmHg ± se 3.3, sunflower oil (155.1 ± se 6.6) and standard diet group (159.0 ±se 4.2). Thus dietary linseed oil suppressed renal and aortic prostaglandin synthesis but did not accentuate renal hypertension, and linoleic acid supplementation did not protect against 1 kidney 1 clip renal hypertension.