Aggression persists after ovariectomy in female rats

Aggression occurs not only in males but also in females, however, under different sex-specific stimulus and endocrine conditions. After being housed with males, female rats exhibit frequent and intense aggressive behavior toward unfamiliar rats. However, the female residents primarily attack female intruder rats, while the male residents attack males and not females. Altering the hormonal condition of the intruders can modify the behavior that they provoke from the residents. Castration of the male intruders reduces aggression from male residents, but ovariectomy of the female intruders does not alter the behavior of the female residents. Treatment of the gonadectomized intruders with gonadal steroids significantly alters the response of the male residents. Resident-intruder aggressive behavior depends on the presence of the testes in the male residents but not on the ovaries or on lactation in the female residents. Even 7 weeks after ovariectomy the female residents continue to show aggressive behavior toward female intruders. In the same time period the castrated male residents show a marked decrease in aggressive and sexual behavior.     

The nonsuppressibility of plasma cortisol persists after pregnancy

To determine if normal balance is restored to the hypothalamic-pituitary-adrenal axis after pregnancy, we compared the dexamethasone suppressibility of plasma cortisol in women four days after delivery of their infant, with that of nonpregnant women. Plasma concentrations of cortisol before dexamethasone administration were similar in the post-partum women and in women taking oestrogen contraceptives, but both were higher than in normally cycling women. After dexamethasone, plasma cortisol in the post-partum women was significantly higher than in both oestrogen-taking and normally cycling nonpregnant women. The reduced dexamethasone-suppressibility of plasma cortisol, which is characteristic of pregnancy, extends into the post-partum period.     

Reduced renal plasma clearance does not explain increased plasma asymmetric dimethylarginine in hypertensive subjects with mild to moderate renal insufficiency

Plasma concentrations of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) increase already in the early stages of renal insufficiency. There is no agreement as to whether reduced renal plasma clearance (RPCL) contributes to this increase. Therefore, we investigated the relationship between estimated glomerular filtration rate (eGFR), RPCL, and plasma ADMA and SDMA in essential hypertensive patients with mild to moderate renal insufficiency. In 171 patients who underwent renal angiography, we drew blood samples from the aorta and both renal veins and measured mean renal blood flow (MRBF) using the (133)Xe washout technique. RPCL was calculated using arteriovenous concentration differences and MRBF. After correction for potential confounders, reduced eGFR was associated with higher plasma ADMA and SDMA [standardized regression coefficient (β) = -0.22 (95% confidence intervals: -0.41, -0.04) and β = -0.66 (95% confidence intervals: -0.83, -0.49), respectively]. However, eGFR was not independently associated with RPCL of ADMA. Moreover, reduced RPCL of ADMA was not associated with higher plasma ADMA. Contrary to ADMA, reduced eGFR was indeed associated with lower RPCL of SDMA [β = 0.21 (95% confidence intervals: 0.02, 0.40)]. In conclusion, our findings indicate that RPCL of ADMA is independent of renal function in hypertensive patients with mild to moderate renal insufficiency. Unlike the case for SDMA, reduced RPCL of ADMA is of minor importance for the increase in plasma ADMA in these patients, which indicates that increased plasma ADMA in this population is not a direct consequence of the kidneys failing as a plasma ADMA-regulating organ.     

Compensatory renal hypertrophy after nephrectomy in newborn rats]

The process of the kidney compensatory hypertrophy in young rats has been studied after nephrectomy on the 2nd day of life. The intact kidney was investigated by morphometrical and electron microscopical methods from the 1st day till the 3rd month after operation. The kidney compensatory hypertrophy in the early postnatal ontogenesis is accompanied by the acceleration of growth and differentiation of renal structures. The hypertrophy involves three successive steps: (1) functional tension of ultrastructures; (2) expressed hyperplasia and hypertrophy of cells; (3) structural-functional specialization. Among the cellular factors of the kidney compensatory growth at this age, the main role is played by the process of cell hyperplasia.     

Increased plasma level of asymmetric dimethylarginine in hypertensive rats facilitates platelet aggregation: role of plasma tissue factor

This study was designed to explore the role of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, in platelet aggregation in hypertension and its possible mechanisms. Spontaneously hypertensive rats (SHR) and L-NAME-induced hypertensive rats were orally administered with L-arginine (1 g/(kg·day) for 14 days. Systolic blood pressure, platelet aggregation, and plasma tissue factor (TF) level and activity were measured. The plasma concentration of ADMA in SHR was determined. In vitro, platelet-rich plasma isolated from Wistar rats was prepared in order to observe the effect of exogenous ADMA on platelet aggregation and TF level and (or) activity in platelet-rich plasma. In both types of hypertensive rats, systolic blood pressure, platelet aggregation, and the level and activity of plasma TF were elevated compared with corresponding control animals. Plasma ADMA level was also increased in SHR. Treatment with L-arginine, a competitor of ADMA, lowered blood pressure and inhibited platelet aggregation concomitantly with a decrease in plasma TF level and activity in both types of hypertensive rats. We also found that exogenous ADMA promoted platelet aggregation and increased TF level and (or) activity in platelet-rich plasma, an effect that was inhibited by pretreatment with L-arginine. Importantly, the enhanced platelet aggregation induced by exogenous ADMA was reduced by pretreatment with anti-TF antibody. The results suggest that endogenous ADMA may be involved in platelet hyperaggregation status in hypertension, and the facilitation of platelet aggregation by ADMA is related to upregulation of the level and activity of plasma TF.     

Asymmetrical dimethylarginine levels on the implantation success of in vitro fertilization and embryo transfer

The aim of this study was to evaluate the level of asymmetrical dimethylarginine (ADMA) levels before gonadotrophine treatment and on the day of oocytes retrieval in order to determine whether ADMA can be used as a predictive marker for implantation success in in vitro fertilization (IVF) cycles. Forty-four unexplained infertile patients were included in the study. Controlled ovarian hyperstimulation was performed using the recombinant follicle-stimulating hormone (FSH) with the standard long protocol for all patients. ADMA and E2 were measured at the beginning of the ovulation induction and on oocyte retrieval day. The primary outcome was the difference in ADMA levels in implantation positive and implantation negative women. At the beginning of the ovulation induction, the mean ADMA levels were 1553 μmol/L and 1.464 μmol/L in the implantation positive and negative groups, respectively. There was no statistically significant difference between groups (p: 0.90). On the day of oocyte retrieval, the mean ADMA levels were 1173 μmol/L and 1170 μmol/L in the implantation positive and negative groups, respectively. There was no statistically significant difference between groups (p: 0.97). In conclusion, ADMA levels before gonadotrophine treatment and the day of oocytes retrieval cannot be used as a predictive marker for implantation success in IVF cycles.     

Physiological variation in plasma total homocysteine concentrations in rats

Hyperhomocysteinemia was initially related to cardiovascular diseases; but homocysteine (Hcy) metabolism disturbances have more recently associated with a wide range of pathophysiological conditions including age-related diseases, disrupted circadian rhythms and gynaecological disorders. Since in many cases we do not know to what extent animal models are physiologically similar to human ones, this study aimed to track spontaneous variations in rat plasma Hcy concentrations during different physiological processes such as life cycle, 24 hours and estrous cycle. Plasma total Hcy concentrations were accessed by HPLC. Plasma Hcy concentration varied with age and newborns had the lowest values (2.94 +/- 0.47 micromol/L). Rats aged 10 days presented concentration similar to 3 month old animals (6.87 +/- 0.67 and 8.29 +/- 1.55 micromol/L respectively). Values decreased to 6.42 +/- 1.65 micromol/L at 6 months and 4.87 +/- 0.81 micromol/L at 28 months. Concerning circadian variations in Hcy concentration cosinor analysis showed acrophase in young rats at 1:09 pm, but no plasma Hcy circadian variations in aged rats. Female rats showed changes in Hcy concentration during the estrous cycle with higher values during the diestrous I (10.61 +/- 1.81 micromol/L) compared with the estrous (8.47 +/- 1.86 micromol/L) and diestrous II (7.68 +/- 1.58 micromol/L) phases. In conclusion, plasma Hcy concentration varied spontaneously with ontogenic development and during the estrous cycle and presented a circadian rhythm variation in young rats.     

Sleep deprivation reduces total plasma homocysteine levels in rats

Hyperhomocysteinemia has been associated with pathological and stressful conditions and is a risk factor for cardiovascular disease. Since sleep deprivation is a stressful condition that is associated with disruption of various physiological processes, we investigated whether it would also be associated with increases in plasma homocysteine levels. Further, since hyperhomocysteinemia may promote oxidative stress, and we had previously found evidence of oxidative stress in brain following sleep deprivation, we also searched for evidence of systemic oxidative stress by measuring glutathione and thiobarbituric acid reactive substance levels. Rats were sleep deprived for 96 h using the platform technique. A group was killed after sleep deprivation and another two groups were allowed to undergo sleep recovery for 24 or 48 h. Contrary to expectation, plasma homocysteine was reduced in sleep-deprived rats as compared with the control group and did not revert to normal levels after 24 or 48 h of sleep recovery. A trend was observed towards decreased glutathione and increased thiobarbituric acid reactive substance levels in sleep-deprived rats. It is possible that the observed decreases in homocysteine levels may represent a self-correcting response to depleted glutathione in sleep-deprived animals, which would contribute to the attenuation of the deleterious effects of sleep deprivation.     

Both acute and chronic exercise enhance in vivo ethanol clearance in rats

Rates of ethanol clearance were measured at rest and with acute exercise in four groups of female Sprague-Dawley rats. Two groups were trained to run on a motor-driven rodent treadmill at 27 m/min, 1 h/day, 5 days/wk and were given a nutritionally balanced liquid diet; one of these groups received 35% calories as ethanol whereas in the other, sucrose was isocalorically substituted for the ethanol. Appropriate sedentary and nonethanol controls were also used. Clearance of a 1.75-g/kg ethanol dose injected intraperitoneally was determined by measuring ethanol levels in the blood each hour and utilizing these values in the Widmark equation (R. Teschke, F. Moreno, and A. Petrides, Biochem. Pharmacol. 30: 1745-1751, 1981) for calculating whole-body ethanol clearance. Rates of ethanol clearance were determined for each rat at 4 and 7 wk of training. The clearance tests at 4 wk included a 60-min period of running exercise, whereas the tests 3 wk later were conducted at rest. The results indicate that both acute exercise and exercise training can increase rates of in vivo ethanol clearance. In addition, the chronic exercise appeared to increase in vitro ethanol metabolism by hepatic microsomes without altering in vitro hepatic alcohol dehydrogenase activity.     

Biliary amino acid excretion in rats before and after bilateral nephrectomy.

In previous studies it could be shown that after bilateral nephrectomy (NX) the excretory function of the liver is disturbed. To further clarify whether or not this "renohepatic syndrome" is caused by toxic effects of uremia or by competition phenomena between various uraemic toxins an additional aspect was investigated: the biliary excretion of endogenous amino acids. Furthermore, previously it could be shown that renal and hepatic excretory functions overlap. Therefore, the renal excretion of effectively biliary eliminated amino acids (glutamic acid, alanine, tyrosine, isoleucine) is very low and vice versa. That means, that the renal excretion of amino acids with low hepatic elimination (tryptophan, citrulline, lysine, taurine) dominates. The hepatic excretion of amino acids is hardly altered after NX. Remarkably, the removal of both kidneys is followed by a distinct reduction in amino acid plasma concentrations, especially if these concentrations are relatively high in the controls. Interestingly, there is no correlation between plasma concentrations and biliary excretion of amino acids. But the calculation of the bile to plasma concentration ratios of amino acids makes it possible to differentiate three groups of amino acids: Amino acids excreted actively into bile (ratio > or = 1), amino acids with ratios below 1, indicating effective retention, and amino acids with ratios of about 1, whose hepatic handling is passive. After NX these ratios tended to approach 1; low ratios increased and high ratios decreased. That means, active processes involved in excretion or retention are obviously disturbed. These changes could indicate uraemic liver damage as proved regarding influence of NX on hepatic excretion of other endogenous substances and xenobiotics.     

Alveolar epithelial fluid clearance persists in the presence of moderate left atrial hypertension in sheep

The effect of moderate left atrial(LA) hypertension on alveolar liquid clearance (ALC) wasinvestigated in anesthetized, ventilated sheep, surgically prepared tomeasure lung lymph flow as well as hemodynamics. To simulate alveolaredema, 3-4 ml/kg of isosmolar 5% albumin in Ringer lactate wereinstilled into each lower lobe, and ALC was measured. After 4 h of LAhypertension (24 cmH₂O), ALC wassimilar to that in control sheep (31 ± 3% with LA hypertension vs.34 ± 10% with normal LA pressure). Because plasma epinephrinelevels were moderately elevated in the presence of LA hypertension, ALCwas then studied in the presence of LA hypertension following bilateraladrenalectomy. Without endogenous release of epinephrine, ALC wassignificantly reduced compared with normal LA pressure (20 ± 7%compared with 34 ± 10%, P < 0.05). Thus endogenous catecholamines caused a submaximal stimulation of ALC in the presence of LA hypertension. Exogenous administration ofaerosolized ₂-agonist therapywith salmeterol increased ALC in the presence of normal LA pressure buthad no stimulatory effect in the presence of moderate LA hypertension.Therefore, we tested the hypothesis that endogenous release of atrialnatriuretic factor (ANF) may downregulate alveolar epithelialNa⁺ and fluid transport in thepresence of LA hypertension. There was a modest twofold increase inplasma ANF levels after LA hypertension. Additional in vitro studiesdemonstrated that, in the presence of₂-agonist stimulation, ANFdecreased Na⁺ pump activity(Na⁺-K⁺-ATPase)in isolated rat alveolar epithelial type II cells. ANF may downregulatevectorial Na⁺ and fluid transportstimulated by endogenous or exogenous -adrenergic agoniststimulation in the presence of LA hypertension. In summary, ALCcontinues even in the presence of moderate LA hypertension. Aerosolized₂-adrenergic agonist therapysignificantly increased ALC, but only when LA pressure was normal.

     

The effects of nephrectomy and probenecid on in vivo clearance of adenosine-3',5'-monophosphate from rat plasma

The disappearance of [8-³H]-adenosine 3′,5′-monophosphate (cAMP) from plasma of the intact rat has been investigated. Thirty minutes after the i.v. injection of a pulse of [³H] cAMP with 3 μmole cAMP into 300–400 g rats, more than 99% of the isotope had been removed from the plasma. The disappearance of isotope from the plasma was retarded by probenecid (20–200 mg/kg body weight), bilateral nephrectomy and bilateral nephrectomy plus hepatectomy, in increasing order of their effectiveness. Ligation of both ureters did not alter the rate of isotope disappearance. After the pulse injection, the amount of isotope in the plasma and tissues was determined and the ratio, cpm per g wet tissue/cpm per ml plasma, was calculated. Kidney cortex, kidney inner medulla and liver showed the most striking accumulations of isotope with ratios of 250, 19 and 18, respectively. Probenecid produced a dose-dependent reduction in the accumulation of isotope in kidney cortex and liver. Other tissues which showed some, albeit small, accumulation of isotope were heart (2.0), lung (2.9) and small intestine (1.6). From the accumulation of isotope in the various tissues it was estimated that the kidney cortex accounted for 39%, liver 15%, and urinary excretion 5% of the injected dose of isotope in the untreated rat. It is concluded that in the rat, at least, the kidney cortex is the principal tissue involved in cAMP removal (and degradation) from the plasma.     

The role of asymmetric dimethylarginine in the regulation of nitric oxide level in rats with acute renal injury

Nitric oxide (NO) is synthesized from arginine (ARG) by NO synthase (NOS). Asymmetric dimethylarginine (ADMA), a competitive inhibitor of NOS, participates in the endogenous regulation of NO synthesis. The main amount of ADMA is enzymatically degraded by dimethylarginine dimethylaminohydrolase (DDAH) widely expressed in renal tissue. The aim of our study was to compare the changes in DDAH activity and ARG synthesis in kidneys, ADMA and ARG concentration in plasma and their urinary excretion under physiological conditions and in acute renal injury (ARI) induced by glycerol in rats. Urinary nitrite/nitrate excretion (NOx) was estimated as an indicator of whole-body NO synthesis. DDAH activity was decreased, ADMA excretion was increased and plasma ADMA did not change in ARI. Plasma ARG concentration, renal ARG synthesis and urinary NOx excretion were decreased. In conclusion, the diminished enzymatic hydrolysis of the NOS inhibitor ADMA and the reduced synthesis of the NOS substrate ARG might affect NO production in ARI.     

Asymmetric dimethylarginine is not involved in ovariectomy-induced osteopenia in rats

Previous studies have indicated that the plasma concentration of nitric oxide synthase inhibitor, asymmetric dimethylarginine (ADMA), was increased in postmenopausal women. In the study reported here, we tested the relationship between the decrease of bone mineral density (BMD) and ADMA concentration in ovariectomized (OVX) rats. Ovariectomized rats at 8 months of age were treated with 17beta-estradiol (10 or 30 microg/kg of body weight/day, s.c.) or L-arginine (300 mg/kg/day, i.p.) for 12 weeks (n = 10 for each group). Pre- and posttreatment total BMD, posttreatment plasma nitrite/nitrate and ADMA concentrations, and posttreatment BMD in the lumbar part of the spine (L4-L6), femurs, and tibias were examined. Ovariectomy caused a significant decrease in several BMD indexes, which was reversed by estrogen treatment (P < 0.05). Plasma nitrite/nitrate concentration was significantly decreased in OVX rats, but was restored by estrogen treatment (P < 0.05). There were no differences in the plasma concentration of ADMA in OVX or estrogen-treated rats. L-Arginine had no effect on plasma nitrite/nitrate concentration and BMD in OVX rats. These results suggest that ovariectomy does not influence the plasma concentration of ADMA, and that ADMA is not involved in ovariectomy-induced osteopenia in rats.     

Lack of relation between venous plasma total catecholamine concentrations and ventricular arrhythmias after acute myocardial infarction.

Electrocardiographic tracings were recorded continuously to monitor ventricular tachycardia and R-on-T and R-on-apex-T ventricular premature beats, and repeated estimations of venous plasma total catecholamine concentrations were carried out in 26 patients admitted to a coronary care unit with acute myocardial infarction. No relation existed between the increased catecholamine concentrations found in these patients and the incidence of ventricular arrhythmias occurring six to 48 hours after the onset of symptoms.