Castration Lowers and Testosterone Restores Blood Pressure in Several Rat Strains on High Sodium Diets

The objective of this study was to determine the effect of a high sodium diet and prepubertal castration (5-6 weeks) and androgen replacement therapy on blood pressure in male normotensive, borderline hypertensive and hypertensive rats on a high sodium diet between 9-22 weeks of age. The strains used were: Wistar Kyoto-(WKY), spontaneously hypertensive rat-(SHR), and borderline hypertensive rat-(BHR). Castration significantly reduced blood pressure (20-30mmHg) and testosterone replacement in castrated males restored blood pressure in all strains. Plasma norepinephrine (NE) increased with castration in the WKY and SHR strains but decreased in the BHR. However, there was a significant elevation in all strains between the midpoint and endpoint NE values. The high sodium diet did not prevent the blood pressure lowering effect of castration.     

Changes in Creatine Kinase Expression Induced by Exercise in Borderline Hypertensive Rat Hearts

Hypertrophy in hypertensive hearts is associated with increased risk of cardiac morbidity and mortality that is not characteristic of exercised hearts. This study was done to determine whether exercise training of normotensive and borderline hypertensive rats induces the increased myocardial expression of BB and MB isoforms of creatine kinase (CK) that characterizes hypertensive hypertrophy. Spontaneously hypertensive (SHR), borderline hypertensive (BHR), and normotensive Wistar-Kyoto (WKY) rats were subjected to either an 8% sodium chloride diet or swim training to produce myocardial hypertrophy. Both exercise and a high salt diet induced an increase in the combined expression of CK-MB and CK-BB in SHR after 2 months. However, since swimming also exacerbated hypertension in SHR, exercise induced effects on CK were not distinguishable from those of hypertension. In WKY, neither exercise nor a high salt diet induced significant changes in CK isozyme expression. In BHR fed a high sodium chloride diet, significant increases in mean arterial pressure and left ventricular weight to body weight were not associated with changes in CK expression. In contrast, following 10 months of swim training BHR exhibited mild hypertrophy, decreased resting heart rates, and an increase in the combined expression of CK-MB and CK-BB. Therefore, exercise associated with a cardiac training effect in BHR induced changes in CK isozyme expression similar to those in hypertensive hearts.     

Hypertension Is Not Related to Suppressed Lymphocyte Proliferation but to Elevated NO Synthesis in Vascular Smooth Muscle Cells of Borderline Hypertensive Rat

Hypertensive individuals often exhibit immune abnormalities. We have previously reported that spontaneously hypertensive rats (SHR) had a severely depressed lymphocyte proliferation response caused by excessive nitric oxide (NO) from macrophages and vascular smooth muscle cells (VSMC). However, the development of hypertension was not correlated with the lymphocyte depression and elevated NO synthesis in macrophages. In this study, we investigated the effect of hypertension on lymphocytes and the NO synthesis system in borderline hypertensive rats (BHR). BHR became significantly hypertensive after receiving a high sodium diet. The proliferation response of lymphocytes in hypertensive BHR was similar to that of normotensive BHR fed a normal diet or of Wistar Kyoto rats (WKY). NO production in macrophages of hypertensive BHR was not different from that of normotensive BHR or WKY. However, NO production in VSMC was significantly elevated in hypertensive BHR. A positive correlation between blood pressure and VSMC NO production exists in hypertensive BHR. These results suggested that high blood pressure neither affected the lymphocyte function nor influenced the activation of NO synthesis in macrophages. Hypertension, however, may influence the activation of VSMC NO synthesis. In conclusion, hypertension is not causally associated with immune dysfunction as seen in SHR but is related to enhanced NO synthesis in VSMC.     

Effects of high-calorie diet on blood pressure and sodium retention in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats

Previous reports from our laboratory have documented that spontaneously hypertensive rats (SHR) have insulin resistance and that insulin resistance is enhanced by high-caloric diet (HCD) feeding. The aim of this study was to elucidate the effect of HCD on blood pressure and sodium retention in both SHR and normotensive Wistar-Kyoto rats (WKY). SHR and WKY were divided into two groups. One group of rats was fed normal diet (ND). The other rats were fed HCD. After the 8-week feeding period, insulin suppression tests were performed. The animals were individually housed in metabolic cages for the last 2 days of the experiment. Food consumption was recorded for 24 h, and a 24-h urine was collected to calculate the sodium excretory ratio. In both strains, body weight was significantly increased by HCD feeding. Blood pressure was significantly elevated in SHR by HCD feeding, whereas that of WKY was not affected by HCD feeding. In both strains, steady-state plasma glucose (SSPG) during the insulin suppression test was higher in the HCD group than in the ND group. SSPG was consistently higher in SHR than in WKY treated with HCD. Urinary sodium excretion ratio was significantly decreased in SHR by HCD, and plasma potassium concentrations were significantly lower in SHR with HCD than in SHR with ND, whereas those of WKY were not affected by HCD feeding. SHR are more sensitive to the induction of insulin resistance than WKY, resulting in sodium retention and elevation of blood pressure.     

Dietary sodium restriction, blood pressure and sympathetic activity in spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were started at birth on sodium diets ranging from severely deficient (9 mumol) to a regular intake (101 mumol Na+/g food). Blood pressure and sympathetic activity were assessed at 6 and 16 weeks of age. At either age, SHR on 9 mumol Na+ failed to develop hypertension. Spontaneously hypertensive rats on 17 mumol Na+ exhibited significant blunting of the hypertension; SHR on 26 mumol showed a small amelioration. At 6 weeks, basal plasma noradrenaline was similar in SHR and WKY on 9 and 101 mumol Na+, whereas plasma adrenaline was increased in SHR at the lowest sodium level. At 16 weeks, both catecholamines were significantly increased in SHR on the 9 and 17 mumol sodium diet versus SHR on the control diet. Blood pressure responsiveness to noradrenaline was significantly decreased on 9 mumol Na+, but to a similar extent in both strains. In contrast, the blood pressure lowering effect of ganglionic blockade was markedly blunted in SHR on 9 mumol Na+ and to a lesser extent on 17 mumol Na+ (both for percentage and absolute decrease) and 26 mumol Na+ (only for absolute fall); however, this did not occur in WKY over the diet-range used. We conclude that a sodium-deficient diet from birth prevents/blunts the development of hypertension in SHR, at least partly by decreasing the pressor effect of the sympathetic nervous system.     

Modification of total body fat in spontaneously hypertensive rats and Wistar-Kyoto rats by dietary calcium and sodium

Studies have indicated that spontaneously hypertensive rats (SHRs) consuming diets high in calcium (Ca2+) and sodium (Na+) weigh less compared to SHRs consuming diets lower in Ca2+ and Na+ while consuming similar amounts of food. Based on calcium's known effects on lipid metabolism, it was important to determine if manipulations of dietary Ca2+ and Na+ would modify total body fat in the SHR. Fifteen SHRs and 17 Wistar Kyoto rats (WKY) were randomized at 4 weeks of age to three diets varying in Ca2+ and Na+: 2% Ca2+/1.0% Na+, 1% Ca2+/0.45% Na+, and 0.1% Ca2+/0.25% Na+. At 15 weeks of age, blood pressure, body weight, and body composition were determined. Significant differences in body weight, blood pressure, and total body fat were observed between diet groups in both strains. Dietary Ca2+ and Na+ induced favorable changes in total body fat content in both the SHR and WKY.     

Low-sodium diet and alpha-adrenoceptors of renal basolateral membrane in spontaneously hypertensive rats.

To clarify the effect of dietary sodium restriction on the mechanism regulating sodium and water in the development of hypertension, we determined the number of the alpha-adrenoceptors in renal basolateral membrane in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The rats had been fed a low-sodium (0.5%) or normal-sodium (0.4%) diet from 3 weeks of age. The experiments were performed at 6, 8 and 20 weeks of age in both rat groups. Renal basolateral membranes were prepared using Percoll and radioligand binding studies were performed using 3H-prazosin and 3H-rauwolscine. Systolic blood pressure in SHR was already elevated at 6 weeks of age compared with that in WKY rats and rose to hypertensive levels at 8 weeks of age. The sodium balance in WKY rats on both diets decreased at 8 weeks of age, but that of SHR decreased at 20 weeks of age. The maximum number (Bmax) for the alpha 1-adrenoceptor did not differ in any groups of the WKY rats or SHR. Bmax for the alpha 2-adrenoceptors increased at 8 weeks of age in the low-sodium SHR compared with normal-sodium SHR, but did not increase in WKY rats. The data show that the increases in blood pressure in the SHR occur prior to significant increases in the alpha 2-adrenoceptor density of renal basolateral membrane, and that the modulation of alpha 2-adrenoceptor density in SHR differs from that in WKY rats under sodium restriction. The results suggest that renal alpha 2-adrenoceptors in SHR could relate the regulatory mechanism to sodium reabsorption under sodium restriction rather than to the primary cause of the development of hypertension in SHR. There may be the possibility of an abnormality in renal alpha 2-adrenoceptor mechanism in SHR.     

Environmental factor(s) during suckling exert long-term effects upon blood pressure and body weight in spontaneously hypertensive and normotensive rats.

To define the role of nurse and pup strain (spontaneously hypertensive rats: SHR nurses and shr pups; Wistar-Kyoto rats: WKY nurses and wky pups) and dietary salt in nurses and pups (low salt and high salt) upon pup body weight and blood pressure, we cross-suckled shr and wky from birth. Nurses after delivery and pups after weaning received either low- or high-salt diets. Pup body weight indicated that WKY dams were better nurses than SHR and that high salt in the nurse and pup diet decreased body weight. At 7 days, WKY on a low-salt diet normalized shr blood pressure and SHR on a high-salt diet reduced shr blood pressure. At 100 days, pup strain strongly affected blood pressure. Salt sensitivity to pup dietary salt depended upon a low-salt diet in nurses. Salt resistance depended on a high-salt diet in WKY nurses. At 300 days, pup strain accounted for most of the blood pressure variability. However, pup diet, pup strain and nurse diet also affected blood pressure (P = 0.05); the blood pressure of shr on a high-salt diet was higher if the nurse was an SHR on a high-salt diet. Thus, nurse environment modulated shr hypertension throughout life.     

Genetic analysis of blood pressure and sodium balance in spontaneously hypertensive rats

Blood pressure and parameters of sodium balance were measured during the first 16 weeks of life in male Okamoto spontaneously hypertensive rats (SHR, n = 22), Wistar-Kyoto rats (WKY, n = 25), and the F1 (n = 27) and F2 (n = 81) hybrids of the SHR and WKY. Genetic analysis revealed that blood pressure in SHR was controlled by approximately four independent genetic loci and the degree of genetic determination was 64.5%. No difference in blood pressure was discernible before 12 weeks of age between those F2 rats that at 16 weeks had blood pressures either higher or lower than one standard deviation from the mean. Exchangeable sodium was measured sequentially in individual rats of all populations by determining their whole-body radioactivity while receiving 37.5 mM 22Na/23NaCl drinking fluid of constant specific activity as their sole source of sodium. The SHR had consistently higher exchangeable sodium levels than WKY and showed evidence of relative sodium retention during the early developmental phase of hypertension. Sodium intake was higher in SHR than WKY from 4 to 16 weeks of age, although saline preference was the same in both strains. None of these parameters of sodium balance were found to correlate with blood pressure in the F2 population. It is concluded that the heritable abnormalities of sodium balance in SHR appear to represent coincidental inbred characteristics controlled by genetic loci that are unrelated to those loci responsible for the expression of hypertension in this model.     

A high phosphate diet lowers blood pressure in spontaneously hypertensive rats

Plasma phosphate values are significantly lower in spontaneously hypertensive rats (SHR) than in normotensive Wistar-Kyoto rats (WKY). In this study, we increased plasma phosphate in SHR by a dietary phosphate intake and followed the effects on blood pressure. Fifteen male WKY and 15 male SHR were housed from 4 weeks of age up to 26 weeks. At 4 weeks of age all SHR manifested a hypophosphatemia compared with age-matched WKY (F = 62, p less than 0.0003). At 5 weeks of age, the rats were divided into three diet groups: a control group, a group receiving 1.41% (wt/vol) KCl in drinking water, and a group receiving 2% (wt/vol) K2HPO4 X KH2PO4 in drinking water. In the control (F = 16.2, p less than 0.02) and KCl groups, (F = 36.3, p less than 0.03), hypophosphatemia persisted throughout the study. The phosphate-supplemented diet normalized plasma phosphate level in SHR but did not change plasma phosphate level in WKY. As a consequence, no difference in plasma phosphate level between WKY and SHR was present in the group receiving additional phosphate from that time on (F = 1.2, p greater than 0.41). The phosphate-supplemented diet significantly decreased systolic blood pressure in both strains. In phosphate-supplemented SHR, a significant decline in systolic blood pressure was observed from 20 weeks of age on (at 20 weeks of age: 222 +/- 3 mm Hg for control SHR vs 198 +/- 5 mm Hg for phosphate-supplemented SHR; p less than 0.0003).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Dietary Calcium on In Vitro Aortic Tissue Responsiveness to a Hypertensive Factor

It has been proposed that calcium supplementation in the diet is associated with a reduction in blood pressure. In the present study, we investigated vascular tissue sensitivity to a hypertensive factor (HF) in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) fed a high calcium diet, a low calcium diet and a food restricted diet. HF, which has been isolated from erythrocytes, increases blood pressure when injected into normotensive rats and stimulates calcium uptake by aortic rings in vitro. Five-week-old rats were divided into the following groups: SHR and WKY fed a regular diet (1% calcium), SHR and WKY fed a high calcium diet (4% calcium), SHR and WKY fed a low calcium diet (0.02% calcium) and SHR and WKY fed a regular diet (1% calcium) in which food intake was restricted to 65% of ad libitum intake. Food intake, body weight, urine phosphate excretion and blood pressure development were followed for 8 weeks. At sacrifice, plasma levels of calcium and phosphate were determined. Tissue responsiveness to HF was calculated by incubating aortic rings from the rats in the different groups with HF and measuring lanthanum-resistant calcium uptake. A 4-fold increase in dietary     

Combined genealogical, mapping, and expression approaches to identify spontaneously hypertensive rat hypertension candidate genes

Allelic expression in genes has become recognized as a heritable trait by which phenotypes are generated. We have examined gene expression in the rat kidney using genome-wide microarray technology (Affymetrix). Gene expression was determined across 4 rat strains, 3 hypertensive spontaneously hypertensive rat (SHR) substrains (SHR-A3, SHR-B2, and SHR-C), and a normotensive strain (Wistar-Kyoto [WKY]). Expression measurements were made in multiple animals from all strains at 4 time points (4 weeks, 8 weeks, 12 weeks, and 18 weeks of age), covering the prehypertensive period in SHR (4 weeks), and the period of rapidly rising blood pressure (8 and 12 weeks) and of sustained hypertension (18 weeks). Regression analysis revealed a close relationship across all strains during the first 3 time points, after which SHR-A3 became a substantial outlier. SHR-B2 and SHR-C demonstrated a very close relationship in gene expression at all times but also showed increased differences compared with the other strains at 18 weeks of age. We identified genes that were consistently different in expression, comparing all SHR substrains at each time point with WKY. The resulting list of genes was compared with blood pressure quantitative trait loci reported for SHR to refine a number of genes consistently differentially expressed between SHR substrains and WKY, persistently differentially expressed across multiple time points, and located in SHR blood pressure-determinative regions of the genome. Genealogical relationships and SHR substrain intercrosses suggest that genes responsible for heritable hypertension in SHR are shared across SHR substrains. The present approach identifies a number of genes that may influence blood pressure in SHR by virtue of allelic effects on gene expression.     

Differential development of vascular and cardiac hypertrophy in genetic hypertension. Relation to sympathetic function

We compared blood pressure, hindquarter vascular resistance properties, left ventricular weight, and norepinephrine kinetics, in spontaneously hypertensive rats (SHR) and weight-matched normotensive Wistar-Kyoto (WKY) rats at 4, 9, 14, 20, 30, and 50 weeks of age. At 4 weeks, systolic and mean blood pressure measurements were the same in both strains, but the vascular resistance of the fully dilated hindquarter bed was significantly higher in SHR than in WKY rats, with a much larger difference during maximum constriction. Plots of resistance at maximum dilatation and at maximum constriction against body weight suggest that a component of the increase in vascular muscle mass in SHR occurred in the neonatal period preceding hypertension followed by a later component related to the rise in blood pressure. By contrast, left ventricular hypertrophy was minimal at 4 weeks and most of its development paralleled the rise in blood pressure. Sympathetic activity, assessed by norepinephrine fractional rate constant, was higher in SHR than in WKY rats in the left ventricle and kidney through most of the period between 4 and 50 weeks, but was similar in both strains in the muscle bed. This pattern of sympathetic activity will accentuate hypertension once cardiac and vascular hypertrophy are fully established. In all regions, norepinephrine tissue concentration was higher in young SHR and could potentiate the trophic effects of growth factors in early vascular hypertrophy. We suggest that the initial (primary) component of vascular hypertrophy precedes the rise in blood pressure and may be critical in the pathogenesis of hypertension. Possible reasons for the short delay in the rise in blood pressure in young SHR, once the vascular "amplifier" has been established, include high vascularity, immaturity of smooth muscle, and delay in the development of left ventricular hypertrophy.     

Possible involvement of atrial natriuretic factor in the antihypertensive action of a high-calcium diet in spontaneously hypertensive and Wistar-Kyoto rats

The present study was designed to determine the possible involvement of atrial natriuretic factor (ANF) in the hypotensive action of a high-calcium diet. The effects of increased dietary calcium (2.9% calcium, HCa) on blood pressure, urinary sodium excretion, and ANF were examined in 30 spontaneously hypertensive rats (SHR) and 30 Wistar-Kyoto rats (WKY). Control groups of 30 SHR and 30 WKY were fed normal calcium lab chow (0.4% calcium, NCa). The HCa diet reduced blood pressure and serum phosphorus concentration and increased urinary excretion of sodium and calcium in SHR and WKY. The HCa diet also caused a sustained increase in plasma ANF concentration and, finally, a decrease in atrial ANF concentration in both groups. A significant inverse correlation was observed between ANF concentrations in plasma and atria of the four experimental groups. Plasma ANF concentration was positively correlated with daily calcium consumption, and blood pressure was inversely correlated with daily calcium consumption in HCa- and NCa-SHR groups and in HCa- and NCa-WKY groups, respectively. Furthermore, a significant inverse correlation between blood pressure and plasma ANF concentration was observed in SHR groups and in WKY groups, respectively. The observed sustained increment in endogenous plasma ANF concentration, which is probably caused by increased secretion from the atrium, may contribute, in part, to the blood-pressure-lowering effects of the HCa diet.     

Elevated Plasma Adrenaline in Spontaneously Hypertensive Rats

Having found that circulating adrenaline (AD) is selectively elevated in stroke-prone spontaneously hypertensive rats (SHRSP) compared with Wistar-Kyoto rats (WKY), we extended the comparison to include other normotensive and hypertensive rat strains. Aortic catheters were implanted in young (5-7 weeks) and old (7-9 months) WKY, Black-Hooded Wistar (BHW), Sprague Dawley (SD), spontaneously hypertensive rats (SHR) and SHRSP for repeated measurement of mean arterial pressure (MAP) and blood sampling under conscious resting conditions. In the young SHR and SHRSP, MAP was already significantly higher than in age-matched WKY but MAP in the SD rats was similar. Plasma AD was significantly higher in SHR and lower in SD rats when compared with WKY. There was no difference in plasma noradrenaline (NA) between strains at this age. At the older age, MAP was 40-60 mmHg higher in SHR and SHRSP than in WKY and BHW but was significantly lower in the SD strain. Circulating AD did not differ between the normotensive strains but was 3-4 times higher in the hypertensive strains. Plasma NA was elevated in SHR only. The acute reduction of MAP caused by ganglion blockade (an index of the sympathetically mediated component of resting blood pressure) was greater in SHR and SHRSP than in WKY at the older age only. However, the residual MAP after ganglion blockade was significantly higher in the hypertensive strains at both ages. Regression analysis showed that in the older rats, plasma AD was correlated with resting MAP, the reduction in MAP with ganglion blockade, the residual MAP and plasma NA. In the young rats, however, plasma AD levels were not correlated with either plasma NA or resting MAP. Thus, even though plasma AD is elevated in the hypertensive strains at an early age, it is not clear whether this increase contributes to the pathogenesis of hypertension.     

Effects of sodium depletion in rats actively immunized against renin

The influence of active immunization against renin on systolic blood pressure in response to a dietary sodium restriction was assessed in normotensive rats (WKY) and spontaneously hypertensive rats (SHR). Immunization was obtained by multiple injections of pure submaxillary murine renin. Animals received a normosalt diet (NS diet) for 6 days. Then sodium was abruptly removed from the diet (LS diet), and rats were maintained for an additional 6 day-period on this salt-free diet. In rats maintained on NS diet, immunization induced a decrease in systolic blood pressure (SBP) about 11 p. 100 and 27 p. 100 respectively in WKY immune and SHR immune groups. SBP was not affected by abrupt dietary sodium removal in non-immunized rats from both strains. However, in immunized rats sodium restriction was accompanied by a significant SBP decrease compared to the value observed during NS period in the same group. The relative variation in SBP was about 10 p. 100 and 14 p. 100 respectively in WKY immune and SHR immune groups. The present study shows that active immunization against renin leads to a reduction in systolic blood pressure regardless to the initial pressure level. When sodium is removed from the diet, systolic blood pressure level is maintained in non-immunized rats, whereas it decreases in immunized rats of both strains. These results confirm the importance of an efficient renin-angiotensin system in the adaptative response to sodium restriction.     

Influence of magnesium on blood pressure and the effect of nifedipine in rats

The influence of long-term alterations in dietary magnesium intake on blood pressure and on the antihypertensive effect of the calcium antagonist nifedipine was investigated in normotensive Wistar-Kyoto (WKY) and in spontaneously hypertensive rats (SHR). The rats were fed a diet either high (1%), normal (0.1%), or low (0.01%) in magnesium for 12 weeks (WKY) and 20 weeks (SHR), respectively. Nifedipine was added to the diet for 4 weeks in concentrations of 300 and 1000 ppm. Each dose was given for 2 weeks. Plasma and intraerythrocytic concentrations of sodium, potassium, and magnesium were measured before and at the end of nifedipine treatment. Blood was obtained by cardiac puncture. In the WKY and SHR, blood pressure was not influenced by magnesium intake. The blood pressure-lowering effect of nifedipine was most pronounced on normal dietary magnesium and was significantly suppressed in the magnesium-deficient rats. Plasma and intracellular total magnesium concentrations were consistently increased during high and reduced during low dietary intake of the ion. Intracellular sodium concentration increased during magnesium deficiency and was normalized by nifedipine. The marked and long-term alterations in plasma and intracellular concentrations of magnesium did not influence arterial blood pressure levels in either the normotensive WKY or the SHR. Therefore, dietary magnesium intake does not appear to play an important role in long-term regulation of blood pressure in rats. However, magnesium depletion attenuates the blood pressure-lowering effect of nifedipine.     

Brain angiotensin in the developing spontaneously hypertensive rat

There are several factors in the manifestation of high blood pressure in spontaneously hypertensive rats (SHR) which implicate a central role for brain angiotensin II (Ang II). We have measured levels of angiotensin in the brain of SHR and rats of the Wistar-Kyoto strain (WKY). The experiments were carried out in 2-, 4-, 14- and 20-week-old rats. Areas of brain from rats were homogenized and purified with SepPak C-18 cartridges. The levels were measured by radio-immunoassay whose detection limit was 1.95 pg/tube. Significant differences were found between the different age groups and between SHR and controls. In the hypothalamus, there was a consistent elevation of brain Ang II in SHR as compared to WKY in all age groups. Cerebellum also had higher levels in SHR, especially in rats at 2 and 4 weeks of age. Brainstem levels were significantly higher in SHR only in the 14-week-old age group. Plasma levels during these time periods did not differ significantly between the strains. The results demonstrate changes in brain Ang II with development. At an early age, there are high levels of Ang II in the hypothalamus and cerebellum which do not correlate with hypertension but may be important for the development of hypertension. The higher levels of brain Ang II in SHR support the hypothesis that hypertension in SHR is related to brain Ang II activity.     

Cardiovascular responses to acute stress in young-to-old spontaneously hypertensive rats

Age-related changes in circulatory responses to short-term shaker stress were investigated in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Hemodynamics (microspheres) were measured at 8, 24, 48, and 96 weeks of age, and plasma catecholamines were measured at 8 and 96 weeks. At rest, elevated mean arterial pressure was associated with unaltered cardiac index and heart rate in SHR compared with WKY at all ages. Regional blood flow was largely similar in both strains, except for a reduced renal flow in 96-week-old SHR. Cardiac index and most regional blood flow tended to or did decline in both strains between 8 and 96 weeks. Plasma catecholamines were similar in both strains at 8 and 96 weeks. Shaker stress evoked responses similar to defense reactions in both strains. The incremental responses in mean arterial pressure, heart rate, cardiac index, and cerebral, skeletal muscle, and myocardial flow and the decremental responses in splanchnic, renal, and skin flow were greater in SHR than in WKY, particularly at 8 weeks. Most of these responses tended to or did decline between 8 and 96 weeks in both strains. The plasma catecholamine responses were also greater in SHR at 8 and 96 weeks, and they did not differ in either strain between these ages. Thus, circulatory and sympathoadrenal reactivity to acute stress were enhanced in SHR compared with WKY, independently of age.(ABSTRACT TRUNCATED AT 250 WORDS)