Vascular and Cardiac Effects of Stress in Albino Rats of Different Sex and Age Groups

Stress exposure induced similar cardiac effects in male and female infantile rats, but vascular reactions to stress in males were more pronounced than in females. In mature male rats (but not in females), both cardiac and vascular responses to stress decreased in comparison with infantile animals. In adult rats, cardiac effects of stress were more pronounced than the vascular response females demonstrated greater cardiac response and less signifi cant vascular reactions than males. Aging was accompanied by a decrease in the cardiac response and increase in the vascular reaction to stress. These changes were more significant in females than in males. In contrast to infantile and adult animals, old females demonstrated greater vascular response to stress than male rats. The observed sex-dependent changes in the ontogeny of vascular and cardiac response to stress are discussed in light of sex- and age-related peculiarities of hypertension development.     

Role of sex, gonadectomy and sex hormones in the development of nitric oxide inhibition-induced hypertension

In this study we have evaluated the influence of sex, gonadectomy and sex hormones on the development of L-NAME-induced hypertension in the rat, focusing our investigation on blood pressure (BP), plasma renin activity (PRA), cardiac hypertrophy and proteinuria. Three experiments were performed to investigate: (i) the influence of sex on the development of L-NAME-induced hypertension; (ii) the effects of gonadectomy on the dimorphism of L-NAME-induced hypertension; and (iii) the effects of testosterone in ovariectomized female and of 17beta-oestradiol in orchidectomized male rats. Male L-NAME-treated rats had higher BP values than females. Orchidectomy of L-NAME-treated rats reduced BP to the levels of females and ovariectomy did not affect hypertension in females. Oestrogenized and orchidectomized males had a BP level similar to intact female L-NAME-treated rats. However, androgenization and ovariectomy did not change BP in female L-NAME-treated rats. PRA was greater in intact male L-NAME hypertensive rats than in female rats, and gonadectomy protected against the increase in PRA such that PRA was similar among all the groups. Intact female hypertensive rats showed significantly greater ventricular hypertrophy compared with male hypertensive rats. Male L-NAME hypertensive rats had increased proteinuria that was not present in female rats. Moreover, testosterone increased proteinuria in males and females regardless of the BP level. Male L-NAME-treated rats developed higher BP, PRA and proteinuria than female rats, but were more resistant to the development of cardiac hypertrophy. The higher PRA of male L-NAME-treated rats might be involved in the sex-dependent dimorphism of this model of hypertension.     

Sex-difference in the age related change of cholesterol metabolism in rats

In Sprague-Dawley rats at the ages of 5 weeks (young) and 9 months (adult), the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in age-matched animals was significantly higher in females than in males. The magnitude of the age-related decrease in the reductase activity was also greater in female rats. When rats were fed a cholesterol-enriched (1%) diet for 30 h as cholesterol challenge, the reduction of reductase activity depended more on sex than on age. The activity of cholesterol 7 alpha-hydroxylase was also higher in female than in male rats and it apparently remained unchanged with age in female rats while it decreased in male rats. With a cholesterol-enriched diet, the hydroxylase exhibited a significant age- and sex-dependent difference and it increased only in young males and adult females. In male rats, the concentration of hepatic cholesterol was significantly higher in adult than in young rats while it was comparable in female rats. The increase in hepatic cholesterol with dietary cholesterol was observed only in male adult rats. A significant age-related difference was observed in the concentration of serum cholesterol. The results suggest an existence of sex-dependent compensatory mechanism for maintenance of hepatic cholesterol homeostasis with age.     

Spontaneous hypertension and hypertensive renal disease in the fawn-hooded rat.

The fawn-hooded (FH) rat, a strain characterized by a platelet storage-pool disease, developed focal and segmental glomerulosclerosis at the age of 2-3 months (males) and approximately 6 months (females). Male animals died spontaneously at 11-13 months, and females at 15 months of age, both with overt malignant nephrosclerosis. During the first half year of life focal glomeruli showed depositions of IgG, IgA, IgM, C3 and fibrinogen in a segmental pattern and mainly in mesangial areas. Mesangial IgG and IgA were already demonstrable at the age of 5 weeks. On electron microscopy no electron-dense deposits suggestive of immune complexes were found. Mean arterial blood pressure in 5.5-month-old male FH rats was increased compared with that of matched Wistar rats. One-year-old FH rats had severe hypertension. The presumed relationship between the hypertension, the renal lesions and the blood platelet defect is discussed.     

Spontaneous hypertension and hypertensive renal disease in the fawn-hooded rat

The fawn-hooded (FH) rat, a strain characterized by a platelet storage-pool disease, developed focal and segmental glomerulosclerosis at the age of 2-3 months (males) and approximately 6 months (females). Male animals died spontaneously at 11-13 months, and females at 15 months of age, both with overt malignant nephrosclerosis. During the first half year of life focal glomeruli showed depositions of IgG, IgA, IgM, C3 and fibrinogen in a segmental pattern and mainly in mesangial areas. Mesangial IgG and IgA were already demonstrable at the age of 5 weeks. On electron microscopy no electron-dense deposits suggestive of immune complexes were found. Mean arterial blood pressure in 5.5-month-old male FH rats was increased compared with that of matched Wistar rats. One-year-old FH rats had severe hypertension. The presumed relationship between the hypertension, the renal lesions and the blood platelet defect is discussed.     

Age, sex and reproductive status alter the severity of anorexia in zinc deficient rats

Food intake and body weight gain in rats fed a zinc-deficient diet are reported. The severity of zinc deficiency-induced anorexia was observed to be dependent upon the age, sex and reproductive status of the animal. Rapidly growing rats such as weanlings, adult males, or ovariectomized females demonstrated more rapid induction of anorexia and more severe effects on cumulative food intake and body weight gain when fed zinc-deficient diets than did slowly growing (nonpregnant female adult) rats given the same diet. These results suggest that feeding in zinc-deficient animals is not regulated by dietary zinc concentration alone, but rather is mediated by one or several as yet undefined factors.     

Plasma renin activity and in vitro synthesis of aldosterone by the adrenal glands of rats with spontaneous, renal, or pinealectomy-induced hypertension.

In the present study a comparison was made on the role of the renin-aldosterone system in rats with various forms of experimental hypertension (pinealectomy-induced, renal and spontaneous). The plasma sodium and potassium concentrations as well as renin activity were measured. The in vitro production of aldosterone by quartered adrenal glands of these rats was also determined. 5 weeks after the operations the blood pressure of the pinealectomized and renal operated rats was significantly increased. The plasma sodium concentration did not differ in various groups, but that of potassium was decreased in the renal hypertensive animals. The plasma renin activity of the pinealectomized rats was elevated while in other forms of hypertension it was at the control level. The basal aldosterone production by the adrenal quarters was equal in all the groups. ACTH, dibutyryl cyclic adenosine-3',5'-monophosphate (DBA) and 5HT stimulated the aldosterone production. The responses to ACTH and DBA were greater in the adrenals of renal hypertensive rats than in the other forms of hypertension or in the controls. We suggest that the renin-aldosterone system is of importance in the maintenance of renal hypertension, while in pinealectomy-induced hypertension elevated plasma renin activity reflects an increased sympathetic activity which probably is the main cause of hypertension in these animals.     

Influence of circadian time, ageing, and hypertension on the urinary excretion of nitric oxide metabolites in rats

Urinary excretion of NO metabolites (NOx) was measured in male spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto controls (WKY) in two age groups: young (11 weeks) and old (58 weeks). Urine was collected every 6 h throughout 24 h with and without injection interperitoneally of N(G)-nitro-L-arginine-methyl-ester (L-NAME), 30 mg/kg, at 7:00 or 19:00 h. In addition, blood pressure changes by L-NAME were evaluated using radiotelemetry. In both strains of rats, injection of L-NAME abolished almost completely the urinary excretion of NOx, indicating that urinary NOx indeed reflect the endogenous rate of NO synthesis. Time-dependent variation in urinary NOx excretion was observed in WKY rats of both ages (analysis of variance, P<0.05), with higher excretion in the dark period. In SHR rats, time-dependent variation in NOx excretion was lost, and the overall amount of NOx excreted within 24 h was significantly lower in young SHR than in age-matched WKY rats. Moreover, blood pressure increases by L-NAME were significantly smaller in SHR than in WKY rats. In old rats of both strains, NOx excretion was reduced, and the difference between the strains disappeared. Our findings demonstrate that ageing is accompanied by a loss in NOx excretion, and suggest that hypertension in SHR leads to a reduction in NO synthesis already at young age.     

The distribution time of intravenously injected raffinose and inulin in intact animals and the effect thereon of sex and infusion of oxytocin.

1. In anaesthetized dogs whose renal pedicles were ligated the distribution time for I.V. administered raffinose was noted. In males the plasma concentration of raffinose fell for 7-10 min from the time of injection and in females it fell for 12-15 min; thereafter in both sexes the plasma concentration remained constant. 2. During I.V. infusion of oxytocin 10 mug/kg. min, the distribution time for raffinose was 12-16 min in males and 4-6 min in females. 3. During the period before stabilization of plasma concentration the concentration of raffinose was higher in the femoral artery than in the vein in both sexes. 4. In anaesthetized rats whose renal pedicles were ligated the distribution time for I.V. injected inulin was 7-8 min in males and 5 min in females. 5. Following alpha-adrenoceptor blockade with phentolamine the distribution time in both male and female rats was 14-15 min. 6. The sex differences in distribution time, both in normal and oxytocin-treated dogs, may be related to the state of contraction and differential sensitivity or pre- and post-capillary blood vessels and hence, of capillary pressure.     

Urinary and renal kallikrein in hypertensive fawn-hooded (FH/Wjd) rats

Urinary excretion of kallikrein (UKal), sodium, potassium, protein, and creatinine, as well as the kidney content of kallikrein and renin, was studied in spontaneously hypertensive FH/Wjd (FH) male and female rats and in age- and sex-matched normal Wistar rats. With the exception of 1-month-old rats UKal excretion was significantly lower in FH rats than in Wistar rats. FH females also excreted less UKal than Wistar females. No UKal inhibitor or increased degradation of this enzyme in the urine of FH rats was detected. There was no difference in creatinine clearance, blood urea nitrogen, or serum electrolytes, and calcium between 5-month-old FH and Wistar males. Wistar rat kidneys contained about twice as much kallikrein as FH rat kidneys. From the age of 2 months FH males excreted more sodium, as well as urine, than all other groups. No differences in potassium excretion were observed. Only FH males, 4 months and older, developed proteinuria. FH males and females became hypertensive at the ages of 2 and 4.5 months, respectively. Plasma renin activity, as well as renal renin activity, was significantly lower in FH than in Wistar males. In conclusion, the decrease in UKal activity which precedes the onset of hypertension suggests that the abnormality in the renal kallikrein system may be involved in the pathogenesis of hypertension in FH rats.     

Sex,age and shock-intensity as factors in passive avoidance

Sex, age and shock-intensity were studied in a step-through passive avoidance test. In adult rats (140 days) males showed more inhibition of a previously punished approach response. No sex differences were observed in young adult animals (60 days). In prepuberal animals (30 days), on the other hand, it was the females which showed more response inhibition. In prepuberty females showed far more response inhibition than in adulthood. Even when using 1.6 mA as a reinforcer, only 17% of the adult females showed inhibition after punishment of the entering response.     

Preventive dietary potassium supplementation in young salt-sensitive Dahl rats attenuates development of salt hypertension by decreasing sympathetic vasoconstriction

Aim: Increased potassium intake attenuates the development of salt‐dependent hypertension, but the detailed mechanisms of blood pressure (BP) reduction are still unclear. The aims of our study were (i) to elucidate these mechanisms, (ii) to compare preventive potassium effects in immature and adult animals and (iii) to evaluate the therapeutic effects of dietary potassium supplementation in rats with established salt hypertension. Methods: Young (4‐week‐old) and adult (24‐week‐old) female salt‐sensitive Dahl rats were fed a high‐salt diet (5% NaCl) or a high‐salt diet supplemented with 3% KCl for 5 weeks. The participation of vasoconstrictor (renin‐angiotensin and sympathetic nervous systems) and vasodilator systems [prostanoids, Ca²⁺‐activated K⁺ channels, nitric oxide (NO)] was evaluated using a sequential blockade of these systems. Results: Preventive potassium supplementation attenuated the development of severe salt hypertension in young rats, whereas it had no effects on BP in adult rats with moderate hypertension. Enhanced sympathetic vasoconstriction was responsible for salt hypertension in young rats and its attenuation for potassium‐induced BP reduction. Conversely, neither salt hypertension nor its potassium‐induced attenuation were associated with significant changes of the vasodilator systems studied. The relative deficiency of vasodilator action of NO and Ca²⁺‐activated K⁺ channels in salt hypertensive Dahl rats was not improved by potassium supplementation. Conclusions: The attenuation of enhanced sympathetic vasoconstriction is the principal mechanism of antihypertensive action exerted by preventive potassium supplementation in immature Dahl rats. Dietary potassium supplementation has no preventive effects on BP in adult salt‐loaded animals or no therapeutic effects on established salt hypertension in young rats.     

Effects of sex,age, weight,and heredity on blood pressure in baboons

Using data on a population of 498 pedigreed baboons, the effects of several covariates, including sex, age, weight, and subspecies, on arterial blood pressures were studied. Females had significantly higher systolic and diastolic arterial blood pressure than males. Both systolic and diastolic arterial blood pressures increased significantly with increasing weight, and for diastolic pressure, the increase was significantly greater in females than in males. Systolic arterial blood pressure significantly decreased with increasing age and the decrease was larger in males. There were significant differences in arterial blood pressures that corresponded with degree of subspecies admixture. © 1995 Wiley-Liss, Inc.     

The effect of sodium load on the development of hypertension, plasma renin and kininogen in rats with renal artery constriction

Effects of sodium load on the development of hypertension, plasma renin activity (PRA) and kininogen were studied in rats with renal artery constriction and untouched contralateral kidney. After the operation or sham-operation, 0.9% NaCl or water were given as drinking fluid. A marked hypertension (systolic pressure greater than 150 mmHg) developed in all operated rats on saline, but only in 2/3 of operated rats on water. In none of the sham-operated controls did systolic pressure exceed 150 mmHg during 7 postoperative weeks. Within the operated group on water, hypertensive rats had significantly higher PRA values than normotensive animals (P less than 0.05). Salt load slightly suppressed the PRA in sham-operated rats but not in animals with constriction renal artery, compared to sham-operated controls on water. The operated rats on salt excess had higher plasma kininogen levels than the operated normotensive rats on water (P less than 0.05), but there were no other significant differences in kininogen values between different study groups, regardless of whether blood pressure was increased or not. The results indicate that in this form of hypertension, the high blood pressure can be maintained without any increase in PRA if animals are subjected to a sodium load which sensitizes vascular beds to angiotensin. The increase in plasma kininogen, suggesting suppression of kallikrein-kinin system, is unlikely associated with the increase of blood pressure.     

Plasma levels of growth hormone correlate with the severity of pathologic changes in the renal structure of aging rats.

It is well known that pharmacologic administration of growth hormone (GH), prolactin (Prl) or adrenal steroids can induce nephrosclerotic lesions in rodents. In this study we correlated circulating levels of endogenous GH, Prl, and corticosterone with the degree of structural nephropathy in rats of different ages. Female young (3 to 4 months), old (25 months), and senescent (33 to 35 months) and male young (3 to 4 months) and old (24 to 26 months) Sprague-Dawley rats were used. Sequential blood samples were removed through intraatrial cannulas while the animals remained conscious and undisturbed. Plasma Prl showed a 3-fold increase in old compared with young males, while old and senescent females displayed a 13- and 64-fold increase, respectively, for Prl. Plasma GH decreased significantly in old compared with young males, while senescent females had elevated GH levels compared with their young and old counterparts. Plasma corticosterone showed an age-related decline in females but not in males. The kidneys from old males showed a marked degree of glomerular sclerosis and obliteration. The presence of tubular metaplasia of Bowman's capsule as well as deposits of iron in the tubular epithelium was common in old males but rare in old and senescent females. There was a strong correlation of plasma GH, but not Prl, with the severity of renal histopathology. Plasma corticosterone showed an inverse correlation with the severity of renal histopathology in old males and senescent females. These results are consistent with the hypothesis that GH contributes to nephrosclerosis of aging rats, whereas the role of corticosterone and Prl in the pathogenesis of these lesions remains unclear.     

Sexually dimorphic cognitive style, female sex hormones, and cortical nitric oxide

Recent studies using the water maze (WM) found marked sex differences in behavioral strategy employed in place learning tasks in adult rats. When a change in the platform position is introduced following learning the place of a platform (visible or hidden) in a different position, female rats escape to the newly positioned visible platform faster than males. Nitric oxide (NO) is implicated in place learning, and there are regional sex differences in its stable metabolites, NO(2)(-)+NO(3)(-), in rat brain. Furthermore, NO(2)(-)+NO(3)(-) levels are sensitive to ovariectomy in female rats. The effect of sex hormones on brain development and function is well documented. The present study was undertaken to study the effects of ovariectomy and hormonal manipulations on cognitive performance in a WM task designed to test differences in behavioral strategy in Sprague-Dawley rats (n=48) of both sexes. Some of the females rats were ovariectomised and received either hormone replacement (estrogen or progesterone alone or in combination) or the vehicle. Cortical and hippocampal NO(2)(-)+NO(3)(-) levels were determined after behavioral testing. There were no group differences in cognitive ability or non-cognitive factors such as motivation or swim speed. Males and intact females differed in their cognitive style, but hormonal manipulations in female rats did not affect this relative use of behavioral strategy. There was a correlation between performance on the trial where sex differences were most prominent and NO(2)(-)+NO(3)(-) levels in the cortex. Our results suggest that the activational effects of circulating gonadal hormones do not play a major role in sexually dimorphic cognitive styles.     

深圳市体检人群代谢综合症及其相关危险因素的分析

目的探讨深圳市体检人群不同性别、年龄组代谢综合症（MS）诊断及其相关危险因素流行病学分布特点。方法按照2004年中华医学会推荐诊断标准,对收集到的8884名体检人员的体重、身高、血压、空腹血糖及血脂进行不同性别、年龄组MS诊断及其相关危险因素流行病学分布特点分析。结果 MS患病人数1412,总患病率为15.89%,其中男性患病率为19.98%,女性患病率为11.52%,患病率在50岁之前,男性明显高于女性,61岁以后女性高于男性,差异均有统计学意义（P〈0.05）。高血压患病率男女分别为21.90%、15.17%,高空腹血糖患病率男女分别为7.10%、4.73%,高甘油三酯（TG）患病率男女分别为44.32%、22.10%,高BMI患病率男女分别为39.07%、18.32%,均为男性高于女性,差异有统计学意义（P〈0.05）。高甘油三酯血症、肥胖患病率最高;各代谢危险因素间有相关性（P〈0.001）。结论深圳市体检人群MS患病率高,特别是青年男性、老年女性,主要危险因素为高甘油三酯血症、肥胖。     

Comparison of Changes in Blood Pressure and Dipsogenic Responsiveness to Angiotensin II in Male and Female Rats Chronically Exposed to Cold

In most forms of experimentally induced hypertension in rats, females develop a less severe form of the disease than males. The objective of the present study was to compare the two genders with respect to the development of cold-induced hypertension. The results of the study indicate that both males and females develop comparable elevations of blood pressure and at approximately the same rate. Thus, the blood pressures of both groups increased significantly within 2 weeks of exposure to cold and reached similar maximal levels by the seventh week. The dipsogenic responsiveness of both groups of cold-exposed rats to acute administration of the peptide hormone, angiotensin II (AngII), was increased to approximately the same extent above that of warm-adapted counterparts, suggesting an increase in the responsiveness to AngII in the brain. To assess this possibility, the induction of the oncogene, cFos, was studied in brain following IV infusion of AngII (333 ng/kg/min). Fos-like immunoreactivity (FLI) was greater (p < 0.01) in subfornical organ, supraoptic and paraventricular hypothalamic nuclei of both cold-exposed groups compared to warm-adapted controls. Thus, both male and female rats have similar elevations of blood pressure as well as increased dipsogenic and FLI responsiveness to administration of AngII during chronic exposure to cold.     

Prenatal stress alters cardiovascular responses in adult rats

Environmental factors in early life are clearly established risk factors for cardiovascular disease in later life. Most studies have focused on nutritional programming and analysed basal cardiovascular parameters rather than responses. In the present study we have investigated whether prenatal stress has long-term effects on cardiovascular responses in adult offspring. Female pregnant Sprague-Dawley rats were subjected to stress three times daily from day 15 to day 21 of gestation. Litters from stressed and control females were cross-fostered at birth to control for mothering effects. When the offspring were 6 months old, blood pressure was measured in the conscious rats through implanted catheters at rest, during restraint stress and during recovery. Basal haemodynamic parameters were similar in the different groups but the pattern of cardiovascular responses during stress and recovery differed markedly between prenatally stressed (PS) and control animals. PS rats had higher and longer-lasting systolic arterial pressure elevations to restraint stress than control animals. They also showed elevated systolic and diastolic blood pressure values during the recovery phase. PS rats demonstrated a greater increase in blood pressure variability compared with control animals during exposure to restraint stress, and showed more prolonged heart rate responses to acute stress and delayed recovery than controls. There was no effect of prenatal stress on baroreflex regulation of heart rate. PS females showed a greater increase in systolic arterial pressure and blood pressure variability and delayed heart rate recovery following return to the home cage then did PS males. These findings demonstrate for the first time that prenatal stress can induce long-term, sex-related changes in the sensitivity of the cardiovascular system to subsequent stress.