Control of aldosterone secretion in the spontaneously hypertensive rat.

Adrenal secretion rates of aldosterone, corticosterone, and deoxycorticosterone were studied sequentially in the spontaneously hypertensive rat and the normotensive Kyoto Wistar rat. Steroid secretion was studied at three different ages: 7-8, 11-13, and 22-25 weeks. Also, peripheral plasma levels of aldosterone and plasma renin activity were determined in both the spontaneously hypertensive and the normotensive rats at 7-8 weeks of age. Aldosterone secretion was elevated markedly in dexamethasone-morphine-treated spontaneously hypertensive rats at both 7-8 and 11-13 weeks of age but was not significantly different from control in 22-25-week-old spontaneously hypertensive rats. No statistically significant differences in corticosterone or deoxycorticosterone secretion rates were observed between the spontaneously hypertensive rats and the normotensive Kyoto Wistar controls; however, the data suggested that dexamethasone did not suppress adrenocorticotropic hormone in the 7-8- and 11-13-week-old spontaneously hypertensive rats to the same extent that it did in the normotensive Kyoto Wistar rats. Therefore, aldosterone secretion was reexamined in acutely hypophysectomized 7-8-week-old rats to eliminate completely the influence of the anterior pituitary; no differences in aldosterone, corticosterone, or deoxycorticosterone secretion rates were observed between hypophysectomized spontaneously hypertensive rats and normotensive Kyoto Wistar rats. Moreover, aldosterone secretion in the hypophysectomized 7-8-week-old spontaneously hypertensive rats was reduced markedly compared with that in the intact 7-8-week old spontaneously hypertensive rats, thus confirming the importance of the pituitary in these animals. Determinations of peripheral plasma aldosterone concentration and plasma renin activity in unstressed 7-8-week-old spontaneously hypertensive and normotensive rats revealed that both parameters were depressed significantly in the spontaneously hypertensive rats. Thus, the present data indicate that the renin-angiotensin-aldosterone system is suppressed in the spontaneously hypertensive rat but do not suggest that the system is critically involved in the hypertensive process in these animals     

Angiotensin Converting Enzyme Activity in Strains of Normo- and Hypertensive Rats

The concentration of angiotensin converting enzyme (ACE) in the lung, kidney and plasma of the following strains of rats were investigated: Sprague Dawley (SD), Wistar Kyoto (WKY), spontaneously hypertensive (SHR), stroke prone SHR (SP-SHR) and low blood pressure SHR (LBP-SHR) i.e. SHR whose blood pressures were below 150 mm Hg. The enzyme concentrations in the lung of the hypertensive rats were significantly higher than those of the normotensive rats but the reverse was true for plasma ACE concentrations. The kidney ACE concentrations in the hypertensive rats were also lower than those of the normotensive rats, but the differences were not significant. There were no significant differences in enzyme concentrations between the normotensive SD and WKY. Similar results were obtained with the three sub-strains of hypertensive rats despite the fact that their mean blood pressure (MBP) varied significantly from each other.     

Effects of captopril on the renin angiotensin system, oxidative stress, and endothelin in normal and hypertensive rats

There is substantial evidence suggesting that angiotensin II plays an important role in elevating blood pressure of spontaneously hypertensive rats, despite normal plasma renin activity, and that converting enzyme inhibitors (captopril) can effectively normalize blood pressure in the spontaneously hypertensive rats. One mechanism by which angiotensin II induces hypertension is via oxidative stress and endothelin, as seen in subpressor angiotensin II-induced hypertension. In fact, it has been shown that antioxidants lower mean arterial pressure in spontaneously hypertensive rats. However, the relationship between angiotensin II, oxidative stress, and endothelin in the spontaneously hypertensive rats is still relatively undefined. This study examines the relationship between mean arterial pressure, plasma renin activity, angiotensin II, oxidative stress, and endothelin in spontaneously hypertensive rats compared with normotensive Wistar Kyoto rats, and the effects of captopril on this association. Untreated spontaneously hypertensive rats had increased plasma angiotensin II levels despite normal plasma renin activity, oxidative stress, and endothelin. Captopril treatment in spontaneously hypertensive rats lowered mean arterial pressure, angiotensin II, oxidative stress, and endothelin, and increased plasma renin activity. In contrast, captopril increased plasma renin activity (suggesting effective captopril treatment) but did not significantly alter mean arterial pressure, angiotensin II, oxidative stress, or endothelin of Wistar Kyoto rats. These results suggest that in spontaneously hypertensive rats, angiotensin II is a primary instigator of hypertension, and that captopril selectively lowers angiotensin II, oxidant stress, and endothelin, which in turn may contribute to the blood pressure-lowering efficacy of captopril in spontaneously hypertensive rats.     

Elevation of intraplatelet free Ca2+ in primary hypertension in man and the rat

Cytosolic free Ca2+ concentrations were measured in platelets from hypertensive and normotensive humans and rats with the use of the fluorescent indicator Quin-2/AM. Without external Ca2+ added, no difference was observed between platelets of hypertensive patients and those normotensive subjects or between platelets of spontaneously hypertensive rats and those of the normotensive Wistar Kyoto and regular Wistar rats. In the presence of 0.5-1 mM external Ca2+, the cytosolic free Ca2+ concentrations were higher both in patients with essential hypertension and rats with genetic hypertension than in their respective normotensive controls. These results suggest that primary hypertension is accompanied by a disequilibrium between cellular Ca2+ influx, storage and extrusion. Such a characteristic if present in other excitable cells and in particular in vascular smooth muscle cells may play a major role in the rise of peripheral resistances.     

Effects of hypertension on cardiac performance in rats with myocardial infarction

To determine the effects of hypertension and myocardial infarction on cardiac performance, hemodynamic studies were performed on etheranesthetized, female spontaneously hypertensive rats and on two strains of normotensive rats, Wistar-Kyoto and American Wistar, 26 days after coronary arterial ligation. Baseline measurements of ventricular and arterial pressures and cardiac output (electromagnetic flowmeter) were obtained. Peak cardiac pumping and pressure-generating capacities were determined during a volume load and aortic occlusion, respectively. Infarct size was determined by planimetry. There was a progressive reduction in mean arterial pressure in relation to infarct size in both hypertensive and normotensive rats, but this reduction was twice as great in spontaneously hypertensive rats as in the normotensive rats, such that the arterial pressure of hypertensive rats with a moderate or large infarction decreased to within the “normotensive range.” However, spontaneously hypertensive rats still maintained significantly higher arterial pressures than did normotensive rats at comparable infarct sizes. There was also a progressive reduction in the peak pressure developed during an afterload stress, and this reduction was greater in hypertensive rats than in normotensive rats with a large infarct. Maximal flow-generating capacity was similarly altered in rats with infarction: Peak stroke volume index varied inversely with infarct size and the reduction in this index was significantly greater in spontaneously hypertensive rats than in normotensive rats with a large infarct. Moreover, peak stroke work index was reduced to a greater extent in spontaneously hypertensive rats than in both normotensive strains of rats at any infarct size. Thus, after myocardial infarction, greater reductions in both pressure and flow-generating capacities occurred in hypertensive rats than in normotensive rats.     

Responsiveness of α2-adrenoceptor/I1-imidazoline receptor in the rostral ventrolateral medulla to cardiovascular regulation is enhanced in conscious spontaneously hypertensive rat

Stimulation of α2-adrenoceptor/I1-imidazoline receptors in the rostral ventrolateral medulla decreases the blood pressure via sympathoinhibition. However, alteration of receptor responses in genetically hypertensive rats remains unclear. We examined cardiovascular responses of α2-adrenoceptor/I1-imidazoline receptor agonist and antagonists microinjected into the rostral ventrolateral medulla of conscious spontaneously hypertensive rats and normotensive Wistar Kyoto rats. Injection of 2-nmol clonidine—an α2-adrenoceptor/I1-imidazoline receptor agonist—unilaterally into the rostral ventrolateral medulla decreased the blood pressure, heart rate, and renal sympathetic nerve activity; the responses were significantly enhanced in spontaneously hypertensive rats than in Wistar Kyoto rats. Co-injection of 2-nmol 2-methoxyidazoxan (a selective α2-adrenoceptor antagonist) or 2-nmol efaroxan (an I1-receptor antagonist) with 2 nmol of clonidine attenuated the hypotensive and bradycardic effects of clonidine-only injection. Injection of 2-methoxyidazoxan alone increased the blood pressure and heart rate in spontaneously hypertensive rats, but not in Wistar Kyoto rats. These results suggest enhanced responsiveness of α2-adrenoceptor/I1-imidazoline receptors in the rostral ventrolateral medulla of spontaneously hypertensive rats.     

Effects on Blood Pressure of Cross Circulation Between Spontaneously Hypertensive and Normotensive Rats

In order to examine the role of humoral factors for the development of hypertension in the spontaneously hypertensive rat of the Münster strain (SHR) cross circulation experiments with normotensive Wistar Kyoto rats were performed. Cross circulation between SHR and normotensive rats for 30 min increased mean arterial pressure in the latter by 29,1 ± 7,6 mm Hg (p < 0,01). Transmission of hypertension by cross circulation was abolished by nephrectomy, adrenalectomy, volume depletion or chronic salt restriction in the SHR. It is concluded that hypertension in SHR is caused by a circulating hypertensive agent produced in kidneys and adrenals, the secretion of which can be suppressed by volume or salt depletion     

Lack of Influence of Circulating Adrenaline on Blood Pressure in Normotensive and Hypertensive Rats

The relationship between circulating adrenaline and blood pressure was examined by manipulating plasma adrenaline levels in both normotensive and hypertensive rats: bilateral adrenalmedullectomy was performed in spontaneously hypertensive rats and stroke-prone spontaneously hypertensive rats; adrenaline bitartrate was infused chronically (25-32 μg/kg/h s.c.) into Wistar Kyoto, Sprague Dawley and stroke-prone rats via osmotic minipumps. Arterial and venous catheters were subsequently implanted for direct measurement of mean arterial pressure, blood sampling and drug administration in conscious rats. Adrenaline infusion for 5-6 weeks in Wistar Kyoto rats did not affect resting blood pressure (118 ± 3 versus 119 ± 1 mmHg in controls) even though plasma adrenaline was elevated 12-fold. Plasma noradrenaline was marginally elevated. Blood pressure was also unaffected by adrenaline infusion in Sprague Dawley or stroke-prone hypertensive rats. One week after adrenal medullectomy, plasma adrenaline was reduced 89% in spontaneously hypertensive rats, but blood pressure was unaffected. Ten weeks after adrenal medullectomy in young stroke-prone rats, resting blood pressure was slightly higher (167 ± 2 mmHg) than in control rats (157 ± 2 mmHg), although adrenaline was reduced by 34% in plasma and 67% in adrenal glands. Nitroprusside was infused acutely to lower blood pressure and reflexly elevate plasma noradrenaline. Neither of these responses were affected by chronic adrenaline infusion or adrenal medullectomy. In both adrenaline-infused Wistar Kyoto and medullectomised stroke-prone rats, autonomic blockade reduced blood pressure to a similar extent as in controls, indicating that the degree of sympathetic vasoconstriction was not altered by either treatment. Moreover, pressor responses to i.v. phenylephrine were similar in all groups, indicating that changes in plasma adrenaline did not affect post-synaptic receptor sensitivity. We conclude that elevated plasma adrenaline seen in spontaneous hypertensive rats is unlikely to contribute to their hypertension.     

Abnormal net Na+ and K+ fluxes in erythrocytes of three varieties of genetically hypertensive rats.

Net Na+ and K+ fluxes were measured in Na+-loaded and K+-depleted erythrocytes of three varieties of genetically hypertensive rats. In Okamoto spontaneously hypertensive rats (4 and 10-12 weeks of age), Na+ extrusion was reduced as compared to normotensive controls (Wistar/Kyoto). Na+ extrusion was also reduced in the hypertension-prone substrain of the Hebrew University Sabra rats as compared to the Na+-resistant substrain. K+ fluxes were similar in both groups. In both Okamoto spontaneously hypertensive rats and the hypertension-prone substrain, hypertension was severe and developed rapidly. In the Lyon spontaneously hypertensive rats, in which the blood pressure elevation is less severe than in other genetically hypertensive rats, erythrocyte net Na+ extrusion was the same as in normotensive controls, but net K+ gain was slightly increased. These erythrocyte abnormalities, observed in three varieties of genetically transmitted hypertension of the rat, are in several aspects similar to those previously described in accelerated and benign human essential hypertension. Erythrocyte Na+ and K+ net flux alterations may thus represent biochemical markers of primary hypertension.     

Arterial structural changes with verapamil in spontaneously hypertensive rats.

Reducing pulse pressure might be more powerful than reducing mean arterial pressure to obtain regression of vascular hypertrophy. However, this hypothesis has never been investigated in the conduit arteries of intact hypertensive animals. A group of 4-week-old spontaneously hypertensive rats (SHR) was treated with the calcium-entry blocker verapamil (50 mg/kg) for 16 weeks and compared with untreated SHR and control Wistar Kyoto (WKY) normotensive rats of the same age. At the end of the experiment, intraarterial thoracic aorta blood pressure was measured both in the conscious and anesthetized animals. Carotid artery diameter and stiffness (echo-tracking techniques) and aortic histomorphometry were determined in parallel. With verapamil, pulse pressure, but not mean arterial pressure, was significantly decreased but did not reach the normotensive values. Carotid internal diameter, medial thickness, and collagen content were significantly reduced by comparison with SHR and did not differ from the values of the WKY group. A significant positive and independent correlation was observed between pulse pressure and medial thickness in the overall population. The study shows that, in SHR chronically treated with verapamil, structural changes may be completely prevented without any change in mean arterial pressure. The parallel change in pulse pressure might suggest that mechanosensitive elements within the vascular wall may be selectively sensitive to the dynamic aspects of physical forces and are able to convert frequency and amplitude information into cellular responses that lead to vascular remodeling.     

Functional and metabolic properties in hearts from aged spontaneously hypertensive rats

The effect of long-term pressure overload on myocardial functional and metabolic alterations was investigated in hearts from spontaneously hypertensive rats of 16 weeks (young SHR) and 44 weeks (aged SHR) and age matched normotensive Wistar Kyoto strain rats (young WKY, aged WKY). The hearts were perfused by working heart mode and whole heart ischemia was induced by one-way valve. Following 20 min of ischemia, the hearts were reperfused for 30 min. The heart-body weight ratio in both SHR groups was significantly higher than in the respective age-matched WKY groups. Coronary flow relative to heart weight in both SHR groups was significantly lower than that of the respective age-matched WKY during both preischemic and reperfused periods. There was no significant difference in the recovery rate of cardiac output between young and aged WKY, whereas the young and aged SHR revealed significantly less recovery than their respective age-matched WKY. Tissue creatine phosphate and energy charge in both aged groups were significantly lower than in the young groups. These results indicate that long-term pressure overload increases susceptibility to ischemia and decreases the myocardial reserve presumably resulting from relative ischemia, whereas deterioration was minimal in the normotensive aged rat heart.     

The role of dopamine in the regulation of neurotransmitter release in spontaneously hypertensive rats

The purpose of the present study was to analyze the influence of dopamine on norepinephrine release in resistance vessels in spontaneously hypertensive rats (SHR). Perfused mesenteric vasculature preparations from spontaneously hypertensive rats (7-10 weeks old) and age-matched normotensive Wistar Kyoto rats (WKY) were used to compare the effects of dopamine on both pressor responses and norepinephrine release. Both responses to electrical nerve stimulation were significantly greater in SHR than in WKY rats. Dopamine reduced these responses in a dose-dependent manner in WKY. However, this suppression of responses to electrical stimulation was attenuated in SHR. These results suggest that the enhanced adrenergic transmission in SHR may partly reflect impaired dopamine-mediated inhibition of nerve terminals, which would contribute to the pathogenesis of hypertension.     

Influence of spontaneous hypertension and cardiac hypertrophy on the severity of ischemic arrhythmias in the rat

Summary Cardiac hypertrophy (CH) and hypertension (HT) are major determinants of sudden cardiac death in patients with coronary artery disease. To investigate the hypothesis that CH and HT increase the incidence of severe ventricular arrhythmias in an animal model, we performed a 30-min period of coronary artery ligation in anesthetized spontaneously hypertensive rats (SHR), normotensive Wistar Kyoto (WKY) and Wistar (W) rats. The incidence and duration of ventricular fibrillation resulting from coronary artery occlusion were significantly (p<0.01) increased in hypertensive rats compared to normotensive animals. The calcium entry blocker nicardipine was administered orally to SHR either chronically for 8 weeks (20 mg·kg^–1 twice daily) or acutely as a single dose of 20 mg·kg^–1. After long-term treatment with nicardipine, left ventricular hypertrophy index and systolic blood pressure were significantly (p<0.001) reduced when compared to vehicle-treated SHR, whereas a single administration of nicardipine only decreased blood pressure without affecting cardiac mass. In the long-term nicardipine-treated SHR group, acute coronary artery ligation induced significantly less ventricular fibrillation (p<0.05) and mortality (p<0.001) than in acutely nicardipine-treated or untreated SHR groups. In conclusion, the data suggest that the severity and incidence of lethal ventricular arrhythmias are more elevated in hypertensive than in normotensive rats and this may be related to the myocardial hypertrophic state.     

Enalapril retards glomerular basement membrane thickening and albuminuria in the diabetic rat

Summary This study has evaluated the effects of the angiotensin converting enzyme inhibitor Enalapril on glomerular ultrastructure and albuminuria in normotensive and hypertensive diabetic rats. Streptozotocin-diabetes was induced in Wistar Kyoto and spontaneously hypertensive rats. Enalapril was administered in drinking water in diabetic normotensive, control hypertensive and diabetic hypertensive rats. Enalapril therapy prevented an increase in glomerular basement membrane thickness in diabetic normotensive, control hypertensive and diabetic hypertensive rats without any significant effect on fractional mesangial volume. Enalapril decreased albuminuria in diabetic normotensive, control hypertensive and diabetic hypertensive rats. Thus, enalapril retards the development of glomerular basement membrane thickening and albuminuria in the rat, in the presence or absence of hypertension.     

Evidence for dramatically increased bone turnover in spontaneously hypertensive rats

Using the 3H-tetracycline model, whole-body skeletal bone resorption was compared among male and female spontaneously hypertensive (SHR) rats and normotensive Wistar Kyoto (WKy) and Sprague-Dawley (SD) rats. Immature animals undergoing rapid skeletal growth and bone sculpting showed a tendency for decreased indices of skeletal resorption in females compared with males. By 24 weeks of age, the indices of the rate of resorption and extent of metabolically reactive bone in male rats were decreased a mean of 68% and 74%, respectively, compared with values obtained at 8 weeks. By comparison, values for 24-week-old females decreased only 26% and 56%, respectively, evidence for a significantly elevated level of resorptive activity in mature females compared with males in each of the 3 rat strains. Within-sex comparisons of 24-week-old animals indicated that bone resorptive activity was similar between normotensive male and normotensive female groups. By comparison, the resorptive activity was significantly increased in both male and female hypertensive rats compared with normotensive controls. This condition was exaggerated in female hypertensive rats, which showed an approximate 81% and 44% increase in the indices of rate of resorption and extent of metabolically reactive bone compared with normotensive WKy controls. The results indicate a marked sexual dichotomy in the decline of skeletal bone resorptive activity following maturation and slowing of skeletal growth. They further indicate a significant elevation of whole skeleton bone turnover in male SHR rats and dramatically increased bone turnover in female SHR rats.     

Secretion of LH in spontaneously hypertensive rats

Weights of testes, seminal vesicles, ventral prostate and pituitary, plasma testosterone and LH concentrations, pituitary LH content and concentration, the LH in-vivo response after LHRH administration (1 microgram), and basal and LHRH-stimulated secretion in vitro were analysed in adult male spontaneously hypertensive (SH) and normotensive control (WKY) rats. Spontaneously hypertensive rats showed: testis and pituitary hypertrophy; seminal vesicle and ventral prostate atrophy; increased plasma testosterone and LH concentrations; increased pituitary LH content and concentration; unchanged net increase of plasma concentrations of LH 15 and 45 min after administration of 1 microgram LHRH; and increased basal LH secretion in vitro with a normal response to LHRH stimulation. These results provide evidence that SH rats show increased LH secretion with a normal response to LHRH stimulation. The coexistence of high plasma concentrations of testosterone with seminal vesicle and ventral prostate atrophy suggest a reduction in the effectiveness of testosterone in these structures.     

A defective beta-hydroxylation of dopamine may precede the full development of hypertension in spontaneously hypertensive rats

A possible mechanism of the previously observed increased adrenal dopamine release and tissue content in spontaneously hypertensive rats (SHR) was explored. The following changes in dopamine beta-hydroxylase activity and catecholamines were noted. At age four weeks (normotensive) or 12 weeks (hypertensive), SHR had lower dopamine beta-hydroxylase activity in the adrenals, heart ventricle and spleen than Wistar Kyoto rats. Tissue dopamine beta-hydroxylase activity in Wistar Kyoto rats was increased with age in the atria but decreased in the ventricles and did not change in the spleen. SHR also had reduced right heart atrial dopamine beta-hydroxylase activity in the hypertensive stage and an overall increase in atrial dopamine content even in the prehypertensive state compared to Wistar Kyoto rats. The increase in noradrenaline content seen with age in the right atrium and spleen in Wistar Kyoto rats was not found in SHR, possibly because of concomitantly decreased dopamine beta-hydroxylase activity. An augmented dopamine:noradrenaline ratio in the spleen of hypertensive SHR may also have been related to an abnormality of the synthesis of noradrenaline from dopamine not necessarily reflected by tissue dopamine beta-hydroxylase determination. A defect of beta-hydroxylation, partly attributable to deficient dopamine beta-hydroxylase activity, may thus precede hypertension and contribute to the hyperdopaminergic state found in SHR.     

Effects of diets containing different proportions of macronutrients on longevity of normotensive Wistar rats

The present investigation examined effects of diets containing different proportions of macronutrients on longevity in two substrains of normotensive Wistar rats - Wistar Kyoto (WKY), the most widely accepted normotensive control for spontaneously hypertensive rats (SHR) and Munich Wistar rats (WAM as designated here). Each substrain was divided into five dietary groups composed of 15 rats each. Compared to a baseline diet composed of near equal calories of sucrose, fat, and protein, the remaining four diets were high sucrose-low protein, high sucrose-low fat, low sucrose-high protein, and low sucrose-high fat. Significantly higher systolic blood pressures were found in the two groups of WKY and WAM ingesting the high sucrose diets compared to the other three groups. The high sucrose groups were also hyperinsulinemic. Although only the group of WKY consuming the high sucrose-low fat diet showed a significantly shortened lifespan, the lifespan of WKY positively correlated with systolic blood pressure when data from all dietary groups were combined. WKY and WAM with an average systolic blood pressure exceeding 150 mm Hg had a significantly shorter lifespan than the rats with lower average blood pressure. Accordingly, elevated systolic blood pressure, especially when the blood pressure exceeds 150 mm Hg, significantly shortens lifespan.     

Relation between luteinizing hormone and prolactin pulses in ovariectomized rats with or without dopamine inhibition

GnRH and GnRH-associated peptide (GAP) have been shown to be cosecreted as spontaneous pulses in hypophysial portal blood. In addition, GAP has been proposed as a physiological inhibitor of PRL secretion. The present investigation was performed to determine whether GAP might play a role in the moment to moment regulation of PRL release in the ovariectomized rat. We anticipated that an inverse relation might exist between PRL and LH pulses if GAP is a physiological regulator of PRL and is coreleased with GnRH. Serial blood samples were collected at 6-min intervals over 4 h from ovariectomized rats bearing chronic jugular catheters and were analyzed for plasma concentrations of PRL and LH by RIA. Release patterns were assessed using a pulse detection algorithm. Some animals were pretreated 30 min before blood sampling with domperidone (a dopamine antagonist that does not cross the blood-brain barrier) to unmask PRL inhibitory responses to GAP that might not otherwise be observable in the presence of normal dopamine inhibition. PRL secretory patterns were pulsatile but highly irregular, in contrast to the regular rhythmic patterns of circulating LH. Domperidone treatment significantly increased the number of PRL pulses. PRL pulse amplitudes, and mean PRL concentrations compared to those in vehicle-injected controls. LH pulses after domperidone administration were more frequent, resulting in slightly higher mean LH concentrations. In both vehicle- and domperidone-injected rats, 60-80% of PRL pulses were concordant with LH pulses (concordance defined as PRL and LH peaks occurring within one sample of each other). Assuming that GAP is cosecreted with GnRH, these data fail to support an acute physiological role for GAP during undisturbed PRL release in the ovariectomized rat because the expected relation between PRL and LH pulses in the event of such a role was not observed. To test a role for GAP more directly, domperidone-treated rats were injected with a rabbit anti-GAP serum during serial blood collection. No increase in PRL release was elicited by this treatment, and pulsatile PRL and LH secretion were unaffected compared to those in control animals injected with hyperimmune serum. To determine whether GnRH is the PRL-releasing secretagogue responsible for concordant PRL and LH pulses, some rats were pretreated 4 h before blood sampling with a potent GnRH antagonist, followed by domperidone 30 min before sampling. Treatment with GnRH antagonist virtually abolished LH pulses, but had no effect on PRL pulses.(ABSTRACT TRUNCATED AT 400 WORDS)     

Decreased Na+ K +ATPase Activity in the Aortic Endothelium and Smooth Muscle of the Spontaneously Hypertensive Rats

The activity of Na⁺ K⁺ ATPase in the endothelium and smooth muscle of the aortae of normotensive and hypertensive rats was investigated. The enzyme activity in the endothelium and smooth muscle of the spontaneously hypertensive rats (SHR) was 2.15 ± 0.48 and 12.98±0.99 respectively. These values were significantly lower (P<0.05) than the enzyme activity in the corresponding tissues (10.10 ± 1.78 for endothelium, 20.77 ± 2.54 for smooth muscle) of the normotensive Wistar Kyoto (WKY) rats. However, with the low blood pressure spontaneously hypertensive rats (LBP-SHR) i.e. in those animals whose blood pressures were below 150 mm Hg, the enzyme activity in both tissues was not significantly different from those of the WKY. Since Na⁺ K⁺ ATPase is coupled to the sodium-potassium pump whose activity affects the functions of other pumps, the results indicate that the development of high blood pressure in the SHR may be related to an alteration in the transport of cations across the cell membrane.