Effects of intravenous glycerol on cerebral blood flow and tissue metabolism in acute cerebral ischemia in spontaneously hypertensive rats

The effects of antiedematous agent with intravenous 10% glycerol on cerebral blood flow (CBF) and metabolism were studied in acute cerebral ischemia experimentally induced by bilateral carotid artery occlusion in spontaneously hypertensive rats (SHR). CBF was measured by the hydrogen clearance technique and brain tissue metabolites such as lactate, pyruvate and ATP in the ischemic brain frozen in situ were determined by the enzymatic method. In comparison with saline-infused SHR, the reduction of CBF in the thalamus following carotid occlusion was significantly small in the glycerol treated SHR. Supratentorial ATP concentration in the 3 hr-ischemic brain was reduced in both groups of rats, but its reduction was significantly smaller in the glycerol-infused group than the other. Lactate and lactate/pyruvate ratio tended to be less increased in the glycerol rats, indicating that ischemic metabolism was restrained by the treatment. The present results strongly suggest that intravenous glycerol is effective against acute cerebral ischemia from the view point of cerebral hemodynamic and metabolism.     

Renal transplantation between male and female spontaneously hypertensive rats.

The higher blood pressures of male compared with female spontaneously hypertensive rats (SHR) are the result of the inheritance of different sex chromosomes, although the pathophysiology has not been defined clearly. The reported hypertensive effect of kidneys transplanted from male SHR raises the possibility of a sex-specific renal abnormality, but the effects of transplanting female SHR kidneys have not been studied. To test this hypothesis, single kidneys were transplanted from male SHR into female SHR recipients and vice versa, followed by removal of the native kidneys of the recipients. Male and female SHR that had undergone uninephrectomy were used as controls. After surgery at 14 weeks of age, systolic blood pressures were measured each week until 30 weeks of age. The replacement of a SHR female kidney with a SHR male kidney was not associated with any significant rise in blood pressure, and the replacement of a SHR male kidney with a kidney from a female SHR was not associated with any reduction in blood pressure. These results indicate that the sexual dimorphism of SHR blood pressure is not the result of intrinsic renal differences between males and females and that nonrenal factors would be more likely to explain the blood pressure differences between the sexes.     

Effect of lovastatin on cerebral circulation in spontaneously hypertensive rats

Statins, which are often given to hypertensive patients, reduce the incidence of stroke. However, their effects on the cerebral circulation have been scarcely studied, although lovastatin has been reported to reduce hypertension-induced renal arteriolar hypertrophy. We examined the structure and mechanics of cerebral arterioles and the lower limit of cerebral blood flow (CBF) autoregulation in spontaneously hypertensive rats (SHR) that were untreated (n=9) or treated for 1 month with lovastatin (n=12; 20 mg x kg(-1) x d(-1)) and in untreated Wistar-Kyoto rats (WKY; n=8). We studied the lower limit of CBF autoregulation by repeated measurement of CBF (arbitrary units; laser Doppler) and internal arteriolar diameter (microm; cranial window) at baseline and during stepwise hypotension. Stress-strain relationships were calculated from repeated measurement of internal arteriolar diameter during stepwise hypotension and cross-sectional area (CSA) of the vessel wall in maximally dilated cerebral arterioles (EDTA, 67 mmol/L). Lovastatin slightly reduced mean arterial pressure (treated, 153+/-3 versus untreated, 171+/-5 mm Hg, P<0.05; WKY, 106+/-3 mm Hg) and normalized CSA (treated, 826+/-52 versus untreated, 1099+/-16 microm(2), P<0. 05; WKY, 774+/-28 microm(2)). Stress-strain curves show that lovastatin also attenuated the increase in passive distensibility. Lovastatin had no effect on the external diameter of cerebral arterioles or the lower limit of CBF autoregulation. Our results show that although lovastatin has substantial effects on arteriolar mechanics and wall CSA, it has little effect on internal diameter. This phenomenon may explain its lack of effect on CBF autoregulation.     

Effect of pregnancy on insulin metabolism in spontaneously hypertensive rats

Several lines of evidence suggest that insulin resistance and/or hyperinsulinemia may play an important role in the pathogenesis of hypertension. We studied the effect of pregnancy on insulin metabolism in spontaneously hypertensive rats (SHRs) and in Wistar-Kyoto rats (WKYs) as a control. Pregnancy markedly reduced blood pressure in both strains of rats, but insulin resistance as determined by the hyperinsulinemic glucose clamp (10 mU/kg/min) increased in SHRs and was unchanged in WKYs. The plasma insulin response to an intravenous glucose challenge in SHRs was low and did not change with pregnancy. Therefore, it is suggested that the regulation of blood pressure in these animals is linked to an unknown factor rather than to insulin resistance and hyperinsulinemia. Fetuses from SHRs had a lower body weight and plasma glucose level and higher plasma insulin and pancreatic insulin levels than those from WKYs. Thus, fetal hyperinsulinemia in the SHR may be linked to the development of hypertension in adulthood.     

Striatal glutamic acid and gamma-aminobutyric acid in transient cerebral ischemia in spontaneously hypertensive rats

A massive striatal dopamine release (241-fold increase) was observed in a previous study during acute cerebral ischemia in rats. In this study, extracellular levels of glutamic acid (GLU), gamma-aminobutyric acid (GABA) and lactic acid were simultaneously determined using in vivo brain dialysis in the striatum of spontaneously hypertensive rats during cerebral ischemia and after recirculation. Extracellular GABA levels increased to 932 +/- 75% (mean +/- SEM) of the resting level and GLU increased to 390 +/- 63% during 20 min ischemia. Although ischemia-induced release of GLU and GABA was demonstrated in this study, the degree of increase was smaller than that of dopamine. These findings may be relevant to the pathophysiology of cerebral ischemia in the striatum.     

Ramipril improves hemodynamic recovery but not microvascular response to ischemia in spontaneously hypertensive rats

BACKGROUND: Angiotensin converting enzyme (ACE) inhibition exerts positive effects on the microvasculature of normotensive animals, although this concept is not universally accepted. Recently, ACE inhibitors have been suggested to be useful for rescue in peripheral ischemia. METHODS: We investigated whether chronic treatment with the ACE inhibitor ramipril may have a positive impact on the defective healing response to ischemia that is typical of spontaneously hypertensive rats (SHR). Unilateral limb ischemia was induced in 20-week-old SHR by surgically removing the left femoral artery. Rats were allowed to regain consciousness and then were randomly allocated to treatment with ramipril (1 mg/kg body weight in drinking water) or vehicle for 28 days. RESULTS: The SHR failed to develop reparative angiogenesis in response to ischemia, thus having inadequate perfusion recovery. Ramipril reduced both tail-cuff systolic blood pressure (180 +/- 7 v 207 +/- 2 mm Hg in the vehicle group at 28 days, P < .05) and intra-arterial mean blood pressure (115 +/- 6 v 135 +/- 5 mm Hg in the vehicle group, P < .05). These effects were associated with increased responsiveness to endothelium-dependent vasodilatation by acetylcholine. Treatment with ramipril did not influence muscular capillary and arteriole density but accelerated the rate of perfusion recovery, leading to complete healing within 28 days after surgery. CONCLUSIONS: These results indicate that ACE inhibition by ramipril may be useful for the treatment of peripheral vascular complications in hypertension.     

Effect of ovariectomy on blood pressure and venous tone in female spontaneously hypertensive rats

BackgroundVenous capacitance plays an important role in circulatory homeostasis. A number of reports have suggested an effect of estrogen on venous function. This study tested the hypothesis that ovariectomy would increase venous tone in the female spontaneously hypertensive rat (SHR) via autonomic mechanisms.MethodsFive-week-old female SHR were subjected to sham operation (Sham) or ovariectomy (OVX). At 10 weeks of age, the rats were instrumented for the measurement of arterial and venous pressure. A balloon catheter was advanced into the right atrium. Mean circulatory filling pressure (MCFP), an index of venous tone, was calculated. Mean arterial pressure (MAP), heart rate (HR), and MCFP were recorded from conscious rats. Postsynaptic adrenergic responsiveness was assessed by constructing cumulative dose-response curves to norepinephrine (NE).ResultsMAP was not significantly affected by ovariectomy (Sham 127 +/- 6 mm Hg vs. OVX 130 +/- 3 mm Hg). HR also was not different between groups (Sham 409 +/- 11 bpm vs. OVX 399 +/- 12 bpm). Conversely, MCFP was significantly, but moderately, increased in OVX SHR (Sham 5.2 +/- 0.2 mm Hg vs. OVX 5.9 +/- 0.2 mm Hg). Ganglionic blockade produced marked decreases in MAP, HR, and MCFP in both groups; however, the responses were not different between groups. Infusion of NE caused dose-dependent increases in MAP and MCFP. There were no statistically significant differences in these responses between Sham and OVX SHR.ConclusionEndogenous ovarian hormones effect a small reduction in MCFP. This effect does not appear to be mediated by adrenergic mechanisms.American Journal of Hypertension (2008). doi 10.1038/ajh.2008.237American Journal of Hypertension (2008); 21, 9, 983-988. doi 10.1038/ajh.2008.237.     

Spironolactone improves structure and increases tone in the cerebral vasculature of male spontaneously hypertensive stroke-prone rats

BACKGROUND: Previous studies show that ischemic cerebral infarct size is related to cerebral vessel structure. Spironolactone, a mineralocorticoid receptor antagonist, decreases ischemic cerebral infarct size in male spontaneously hypertensive stroke-prone rats (SHRSP). Therefore, we hypothesized that chronic spironolactone treatment would improve cerebral artery structure in the SHRSP. METHODS: Six-week-old male SHRSP were treated with spironolactone (2.5 mg/day) for 6 weeks and were compared to untreated control SHRSP and normotensive Wistar Kyoto (WKY) rats. Using a pressurized arteriograph, structural measurements of the middle cerebral artery (MCA) were taken under passive (calcium-free), zero-flow conditions. Myogenic tone was calculated from active and passive measurements taken at 75 and 125 mmHg. Mean arterial pressure was measured using radiotelemetry. RESULTS: Myogenic tone was increased only at 75 mmHg in the spironolactone-treated SHRSP compared to control rats. The MCA lumen and outer diameters were increased in the spironolactone-treated SHRSP compared to control SHRSP, but were not different from WKY rats, indicating a decrease in vascular remodeling. There was no effect of spironolactone on blood pressure, suggesting that this is a blood pressure-independent effect. CONCLUSION: Increased myogenic tone and lumen diameter in the spironolactone-treated SHRSP may be responsible for the protective role of spironolactone in ischemic stroke.     

Morphometric study of cerebral arteries from spontaneously hypertensive and stroke-prone spontaneously hypertensive rats.

OBJECTIVE: The importance of sympathetic innervation for the development of structural changes in the cerebral arteries of hypertensive animals was studied. DESIGN: Sympathetic denervation was induced with combined treatment from birth of antibody against nerve growth factor and guanethidine. Previous studies from our laboratory showed that this procedure not only caused a permanent denervation of the mesenteric arteries, but also prevented the development of hypertension in spontaneously hypertensive rats (SHR). METHODS: Morphometric measurement of the structural changes was carried out in the basilar, superior cerebellar, posterior cerebral and middle cerebral arteries from 28-week-old SHR, stroke-prone SHR, and normotensive Wistar-Kyoto rats. The results were compared with those obtained from cerebral arteries of sympathectomized rats. RESULTS: Total vascular wall cross-sectional area was significantly larger in the basilar and superior cerebellar arteries from hypertensive rats compared with normotensives. The change was characterized by an increase in the number of smooth muscle cell layers. There were also differences between the two hypertensive groups in some arteries. Sympathetic denervation attenuated the development of hypertension and vascular changes in some arteries. There was a positive linear correlation between blood pressure and medial cross-sectional area, and between blood pressure and the number of smooth muscle cell layers for the four arteries analysed. CONCLUSION: Sympathetic nerves have a trophic influence upon the remodelling of some cerebral arteries during the development of genetic hypertension.     

Effects of cilazapril on the cerebral circulation in spontaneously hypertensive rats

Chronic hypertension is associated with a lower cerebral vascular reserve due to thickening of the media of cerebral vessels. The goal of the present study was to determine if long-term inhibition of angiotensin converting enzyme with cilazapril, a new long-acting angiotensin converting enzyme inhibitor, could improve cerebral vascular reserve. For this purpose, two groups of 12 spontaneously hypertensive rats were compared. One group was treated with 10 mg/kg/day cilazapril from 14 weeks to 33 weeks of age and was compared with a group treated with placebo. A third group of 12 Wistar-Kyoto rats treated with placebo was used as reference. At the end of the treatment period, cerebral vascular reserve was evaluated by measuring cerebral blood flow (radioactive microspheres) at rest and during maximal vasodilation induced by seizures provoked by bicuculline. Then, the rats were perfusion-fixed, and morphometry of the cerebral vasculature was performed. Cerebral vascular reserve was severely impaired in the spontaneously hypertensive rats since their maximal cerebral blood flow was decreased by 52% compared with the Wistar-Kyoto rats. Cilazapril normalized cerebral blood flow reserve. This normalization was associated with a decreased thickness of the medial layer in the carotid artery, the middle cerebral artery, and in the pial arteries larger than 100 microns. Further studies are required to determine whether this decreased medial thickness is due to the normalization of blood pressure induced by cilazapril or to the reduction of trophic factors such as angiotensin II.     

Rapid metabolic failure in spontaneously hypertensive rats after middle cerebral artery ligation

The metabolic characteristics of the penumbral region were examined in spontaneously hypertensive rats one hour after permanent middle cerebral artery occlusion. The effect of hyperglycemia on this region was examined by providing a glucose load prior to occlusion. The depressed concentrations of adenosine triphosphate and elevated levels of lactate in the penumbral region were similar to those found in the ischemic focus. The purported neuroprotective effect of hyperglycemia in the penumbral region was not reflected in an increased high-energy phosphate level in the penumbral region. The rapid deterioration of the metabolic status of this region in this strain of rat suggests that the increased consistency of infarction may come at the expense of the penumbral region, and thus this model may not be well suited for the study of metabolic changes and perhaps even therapeutic intervention.     

Peripheral dopamine synthesis and metabolism in spontaneously hypertensive rats

We have studied several parameters of peripheral dopamine synthesis and metabolism in spontaneously hypertensive rats during the development of hypertension. Compared to Wistar-Kyoto rats, there was an increased dopamine content in 8-week-old spontaneously hypertensive rats in the adrenals (1.6 +/- 0.1 vs. 1.2 +/- 0.1 nmol/pair in Wistar-Kyoto rats) and kidneys (97 +/- 12 vs. 63 +/- 7 pmol/g tissue in Wistar-Kyoto rats), but the dopamine content in peripheral organs from normotensive 4-week-old spontaneously hypertensive rats did not differ from Wistar-Kyoto rats. In the heart, the dopamine increase was observed in 14-week-old spontaneously hypertensive rats (systolic blood pressure: spontaneously hypertensive rats, 189 +/- 9; Wistar-Kyoto rats, 106 +/- 2 mm Hg;) in both atrium (spontaneously hypertensive rats, 133 +/- 14; Wistar-Kyoto rats, 86 +/- 20 pmol/g tissue) and ventricle (spontaneously hypertensive rats, 41 +/- 6; Wistar-Kyoto rats, 23 +/- 5 pmol/g tissue). Urinary free dopamine and dihydroxyphenylacetic acid, but not norepinephrine or normetanephrine, in spontaneously hypertensive rats significantly increased between the ages of 7 and 11 weeks, reflecting the dopamine changes in tissue and suggesting a selective increase of the rate of dopamine synthesis and release.(ABSTRACT TRUNCATED AT 250 WORDS)     

Brain ischemia and gastric mucosal damage in spontaneously hypertensive rats

Brain ischemia is often accompanied by acute gastric lesions. To clarify the underlying mechanism, the influence of acute ischemic insult to the brain on gastric hemodynamics and mucosal integrity was examined in spontaneously hypertensive rats. One hour after brain ischemia, gastric mucosal blood flow decreased to 71% of the preischemic levels in the control rats but was preserved significantly better, at 94 and 108%, in the prazosin-treated and guanethidine-treated rats, respectively. Vagotomy almost abolished the decrease in gastric mucosal blood flow during cerebral ischemia. Intragastric 0.6 N hydrochloric acid administered just after reperfusion induced more severe hemorrhagic ulcers in the control than in the prazosin-treated and vagotomized groups. These results suggest that noradrenergic neurons acting through ₁-adrenoceptors contributes to the decrease in gastric mucosal blood flow, and the subsequent disturbed integrity of the gastric mucosa, through the vagal adrenergic pathway during brain ischemia in spontaneously hypertensive rats.     

Effect of aspirin on the contractility of aortic smooth muscle in female spontaneously hypertensive rats.

The effects of acetylsalicylic acid (ASA), on aortic smooth muscle contractility during hypertension were studied in female SHR and WKY rats. The rats were administered two intraperitoneal injections of 10 mg/kg of ASA per week for three weeks. Twenty four hours after the last injection the aortic smooth muscles were evaluated for generation of active tension in response to KCl, phenylephrine, clonidine and norepinephrine. We report that aortic rings from ASA-treated SHR animals were more responsive than rings from non-treated SHR female rats. ASA treatment of SHR animals restored the contractile response to the level shown by non-treated WKY control female rats. The response from aortic rings of ASA-treated SHR to KCl, phenylephrine and clonidine was essentially similar to the response of rings from non-ASA-treated WKY control female rats. We did not observe any decrease in the systolic blood pressure during the ASA treatment in SHR female rats. These results suggest that acetylsalicylic acid modulates aortic smooth muscle contractility either through the metabolites of arachidonic acid or through alpha-adrenoceptors.     

Enhanced vasomotion of cerebral arterioles in spontaneously hypertensive rats

Intrinsic rhythmic changes in the diameter of pial cerebral arterioles (30-70 microns) in anesthetized normotensive and hypertensive rats were assessed in vivo to determine if any significant differences exist between the two strains. All diameter measurements were analyzed using a traditional graphic analysis technique and a new frequency spectrum analysis technique known as the Prony Spectral Line Estimator. Graphic analysis of the data revealed that spontaneously hypertensive rats (SHR) possess a significantly greater fundamental frequency (5.57 +/- 0.28 cycles/min) of vasomotion compared to the control Wistar-Kyoto normotensive rats (WKY) (1.95 +/- 0.37 cycles/min). Furthermore, the SHR cerebral arterioles exhibited a significantly greater amplitude of vasomotion (10.07 +/- 0.70 microns) when compared to the WKY cerebral arterioles of the same diameter (8.10 +/- 0.70 microns). Diameter measurements processed with the Prony technique revealed that the fundamental frequency of vasomotion in SHR cerebral arterioles (6.14 +/- 0.39 cycles/min) was also significantly greater than that of the WKY cerebral arterioles (2.99 +/- 0.42 cycles/min). The mean amplitudes of vasomotion in the SHR and WKY strains obtained by the Prony analysis were found not to be statistically significant in contrast to the graphic analysis of the vasomotion amplitude of the arterioles. In addition, the Prony system was able to consistently uncover a very low frequency of vasomotion in both strains of rats that was typically less than 1 cycle/min and was not significantly different between the two strains. The amplitude of this slow frequency was also not significantly different between the two strains. The amplitude of the slow frequency of vasomotion (less than 1 cycle/min) was not different from the amplitude of the higher frequency (2-6 cycles/min) vasomotion by Prony or graphic analysis. These data suggest that a fundamental intrinsic defect exists in the spontaneously hypertensive rat that may contribute to the pathogenesis of hypertension in these animals.     

Effect of blood glucose level in acute cerebral ischemia in spontaneously hypertensive rats--survival and brain pathology

The present study was designed to examine the effect of blood glucose level on survival and pathologic changes of the cortical neuronal cells during and after three-hour incomplete cerebral ischemia, which was induced by bilateral carotid artery ligation in spontaneously hypertensive rats (SHRs). Blood glucose levels were varied by intraperitoneal infusion of 50% glucose (hyperglycemia) or insulin with hypertonic saline (hypoglycemia) or hypertonic saline (normoglycemia). None of the hyperglycemic or normoglycemic animals died during three-hour ischemia, whereas 45% of hypoglycemic animals died (p greater than 0.001). The survival rate for twenty-four hours after recirculation was in the following ascending order: hypoglycemia, normoglycemia, and hyperglycemia. Neither hypoglycemia nor hyperglycemia (38-392 mg/dL) in nonischemic animals developed any morphologic changes in the cerebral cortex. However, both the ischemic and recirculated brains showed various degrees of histologic changes such as shrinkage of the neuronal cells with cytoplasmic vacuoles, perineuronal edema, and swelling of neuropils. Such ischemic damage of the brain was more marked in hypoglycemic animals than in hyperglycemic or normoglycemic ones during ischemia, as well as one hour after recirculation. The results suggest that cerebral ischemia and its outcome become more deleterious in hypoglycemic than in normoglycemic and hyperglycemic states. On the other hand, hyperglycemia is not necessarily a disadvantage in acute cerebral ischemia with or without reperfusion in this model.     

Lipid metabolism in spontaneously hypertensive rats (SHR).

Plasma cholesterol was lower in spontaneously hypertensive rats (SHR), while plasma triglyceride and free fatty acid were increased in comparison with control normotensive Wistar-Kyoto (WK) rats. Correspondingly, [1-14C]-acetate incorporation into liver cholesterol was clearly decreased in SHR as compared with WK. As for lipogenic enzyme activities, glucose-6-phosphate dehydrogenase, malic enzyme and acetyl-CoA carboxylase in SHR were respectively decreased, increased and not significantly different, in comparison with WK rats. Liver cholesterol was rather low and cardiac triglyceride was slightly increased in SHR. Aortic cholesterol and triglyceride levels were not significantly different between SHR AND WK rats. Thus, SHR have an abnormality in lipid metabolism, especially in cholesterol synthesis, but the pathological implication of this in hypertension and related vascular lesions is not yet clear.     

Myocardial energy metabolism in the hypertrophied hearts of spontaneously hypertensive rats

Summary Age-related changes in the myocardial energy metabolism were studied in spontaneously hypertensive (SHR) rats of 5–25 weeks of age. Systolic blood pressure increased rapidly during 5 to 10 weeks of age (developing phase) and attained a plateau level at 10 to 15 weeks (sustained phase). Even during the developing phase, the heart was hypertrophic, as assessed by an increase in the ratio of the ventricular weight to body weight. However, myocardial contents of glycolytic intermediates and high energy phosphate compounds and thus, the myocardial energy state (phosphorylation potential) in SHR rats did not differ from those in age-matched normotensive Wistar-Kyoto (WKY) rats. The lactate/pyruvate ratio was significantly lower in SHR rats. On the other hand, during the sustained phase, cardiac hypertrophy progressed only gradually, and myocardial contents of creatine phosphate and ATP were lower, while the lactate content was higher than in WKY rats. The lactate/pyruvate ratio was elevated, while phosphorylation potential was lowered. These findings suggest that the energy state is normal during the developing phase of hypertension despite the presence of cardiac hypertrophy and the increased pressure load, whereas the energy state is at a lower level during the sustained phase of hypertension.

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Zusammenfassung Die altersabhängigen Änderungen des myokardialen Energieumsatzes wurden bei spontanhypertensiven, 5 bis 25 Wochen alten Ratten (SHR) untersucht. Der systolische Blutdruck stieg zwischen der 5. und 10. Lebenswoche rasch an (Entwicklungsphase) und erreichte nach 10 bis 15 Wochen ein Plateau (Dauerphase). Auch während der Entwicklungsphase war das Herz hypertrophiert, gemessen an einem Anstieg des Verhältnisses Ventrikelgewicht: Körpergewicht. Jedoch unterschied sich der Gehalt des Myokards an Intermediärprodukten der Glykolyse und energiereichen Phosphaten und damit bezüglich des energetischen Status (Phosphorylierungspotential) bei SHR-Ratten nicht von gleichaltrigen normotensiven Wistar-Kyoto-Ratten (WKY). Das Lactat-Pyruvat-Verhältnis war bei SHR-Ratten signifikant vermindert. Andererseits nahm die Herzhypertrophie während der Dauerphase nur allmählich zu; der Gehalt an Kreatinphosphat und ATP war geringer, während der Lactatgehalt höher war als bei WKY-Ratten. Das Lactat-Pyruvat-Verhältnis war gesteigert, während das Phosphorylierungspotential vermindert war. Diese Befunde lassen vermuten, daß der energetische Status während der Entwicklungsphase der Hypertension normal ist trotz des Vorliegens einer Herzhypertrophie und gesteigerter Druckbelastung, während der energetische Status während der Dauerphase herabgesetzt ist.

     

Changes in cardiac beta-adrenoceptor concentrations in spontaneously hypertensive and experimental renal hypertensive rats

Cardiac beta-adrenoceptors were studied in membrane fractions from spontaneously hypertensive rats (SHR) and rats with two-kidney, one clip hypertension (2K, 1C HT), using radioligand binding method. beta-Adrenoceptor concentration measured by [3H]-dihydroalprenolol (DHA) binding was significantly lower in cardiac membranes from two months old SHR than those from Wistar-Kyoto rats (WKY) (38.2 +/- 2.6 vs 45.1 +/- 1.8 fmol/mg protein, means +/- SEM, p less than 0.05). Cardiac membranes from 2K, 1C HT rats had also a lower concentration of beta-adrenoceptors than those from the sham-operated control rats at a week after operation (30.9 +/- 2.2 vs 47.8 +/- 1.6 fmol/mg protein, p less than 0.01). But receptor affinity remained unchanged. These reduced concentrations of beta-adrenoceptors were restored to control levels at 12 months old in SHR and at 6 weeks after operation in 2K, 1C HT rats, although age-dependent decrease in beta-adrenoceptor was observed. The decrease in beta-adrenoceptor was associated with increase in plasma noradrenaline levels during the earlier stages of hypertension. But there is no correlation between beta-adrenoceptor concentrations and plasma noradrenaline levels in the chronic stages of hypertension. No significant difference was found in activities of 5'-nucleotidase, which is a marker enzyme of cell membrane, in membrane fractions between the hypertensive hearts and the controls, suggesting that the cardiac hypertrophy is not a determinant factor for change in beta-adrenoceptor. The observed decrease in beta-adrenoceptor concentration may reflect an increase in sympathetic nerve activity during development of hypertension. In the chronic stages of hypertension, additional factors may be involved in the restoration of beta-adrenoceptors.