摘要:

We have studied the contribution of circulating renin of renal origin to renin-like activity within the arterial wall and to blood pressure. Bolus injections of renin sufficient to elevate blood pressure by 44.7 mm Hg caused aortic renin to rise from 0.13 to 1.48 ng angiotensin 1/100 mg/hr in nephrectomized rats. Elevation of aortic renin was still present at 6 hours, and this was associated with significant blood pressure elevation (p< 0.05) which could be reversed by infusion of sarcosine,1 alanine,8angiotensin II (saralasin). Prevention of the pressor effect by pretreatment with the converting enzyme inhibitor captopril did not reduce renin uptake. When kidneys were left in situ, although significant uptake of renin could be demonstrated 1 hour after injection, the increase at 3 hours was no longer significant (p> 0.05) and blood pressure returned to normal by V/i hours. This change in blood pressure may be related to the much more rapid clearance of circulating renin in the presence of normal kidneys or to other renal factors influencing the blood pressure response. The present studies demonstrate therefore that most of the renin-like activity within the aortic wall is derived from plasma renin and it seems probable that this component of the renin-angiotensin system plays an important role in blood pressure maintenance in the nephrectomized rats injected with renin. The relationship is less obvious in the presence of normal kidneys where additional influences may come into play.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Vascular renln-llke activity was studied in the aortas and the cerebral microvessels of Sprague-Dawley rats and in the aortas of spontaneously hypertensive rats. Methods were employed to maximize detection of tissue renin and to simultaneously minimize contamination of that activity by either plasma renin or nonspecific proteases capable of angiotensin I generation. To this end, renin activity was measured near its pH optimum; plasma renin was eliminated by nephrectomy; and nonspecific proteases such as cathepsin D were either inhibited by proteolytic blockers or removed by chromatography over immobilized bovine hemoglobin. Aortic vascular renin-like activity was detected in rats not subjected to nephrectomy and could be inhibited by preincubation of samples with antimouse renin antibody shown to cross-react and inhibit rat plasma renin activity. Furthermore, vascular renin-like activity disappeared after nephrectomy in parallel with the disappearance of plasma renin activity. In the absence of contaminating enzymatic activities, no tissue renin-like activity could be demonstrated in either aortas or cerebral microvessels of Sprague-Dawley rats or in aortas of spontaneously hypertensive rats.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Sodium (Na+) and potassium (K+) transport by the furosemide-sensitive Na+-K+transport system, the Na+-K+pump, and the cation leak(s) were studied in erythrocytes from DOCwater, DOC-salt, two-kidney, one clip (Sprague-Dawley), and spontaneously hypertensive rats (Wistar- Kyoto). Rubidium (Rb+) was used as a tracer for K+. After 4 weeks of DOC-salt hypertension, inward K+(Rb+) transport by the furosemide-sensitive system was increased threefold, and the inward Na+leak and the red cell Na+content were elevated by about 50%. The rise in cell Na+accelerated K+inward and Na+outward transport by the Na+-K+pump. DOC-water hypertension caused similar but less pronounced changes. In two-kidney, one clip hypertension, the Na+leak and the Na+-K+pump rates were slightly elevated, and furosemide-sensitive Rb+uptake tended to be increased. In spontaneously hypertensive rats, furosemide-sensitive Rb+uptake was accelerated by 50%. The marked hypokalemia in DOC-water and DOC-salt hypertension was associated with a slight loss of red cell K+and an increase in mean cellular hemoglobin content (MCHC), indicative of cell shrinkage. Hypokalemia induced by dietary K+deficiency caused alterations in red cell cation transport, content, and cell volume which were qualitatively similar but more pronounced than those seen in DOC-salt hypertension. Osmotic shrinkage in vitro induced a severalfold acceleration of furosemide-sensitive Rb+uptake, similar to that observed in rat erythrocytes shrunken in vivo in K+- deficient states. It is concluded that the acceleration of furosemide-sensitive K+(Rb+) transport in erythrocytes of mineralocorticoid hypertensive rats is largely caused by the hypokalemia and consecutive red cell K+loss and shrinkage, respectively. Mean cellular hemoglobin content (MCHC) is thus a parameter that must be considered in studies on Na+and K+transport across the membrane of rat erythrocytes.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Captopril infused into the lateral ventricle (ICV) of adult spontaneously hypertensive rats (SHR) decreases blood pressure. The current study was designed to explore the effects of brain converting-enzyme inhibition in young animals before the development of established hypertension and to characterize changes induced by captopril in a variety of pressor systems that might be responsible for the development of hypertension in this strain. Captopril (1.25 μg/0.5 μl/hr) was infused into male SHR starting at 7 weeks of age. Four weeks later systolic blood pressure was only 157 ± 3.3 compared to 181 ± 3.9 mm Hg in vehicle-infused controls, and the pressor effect of ICVinjected angiotensin I was attenuated by 50%. When the same dose of captopril was infused intravenously, hypertension progressed as in vehicle-treated rats. Serum angiotensin-converting enzyme activity (SACE) and plasma arginine vasopressin (AVP) concentration were significantly higher (p< 0.001 and 0.05, respectively), in the ICV captopril group than in the ICV vehicle group, while plasma aldosterone concentration and renin activity, fluid intake, urine volume, and urinary sodium excretion were similar in the two groups. Peripheral sympathetic nervous system activity assessed in the resting state was not altered by captopril treatment. In addition, AVP content of the telencephalon, diencephalon, mesencephalon, and pons medulla were not altered by ICV captopril. Renin activity was elevated in the telencephalon of ICV captopril-treated animals but unaltered in the other brain regions examined. These data demonstrate that ICV administration of captopril attenuates the development of hypertension in young SHR by mechanisms apparently independent of altered fluid and sodium balance and the sympathoadrenal system. The effect on blood pressure occurs in the absence of changes in renin activity or AVP content of plasma or those brain regions most often associated with blood pressure control.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

This study examined the cardiovascular, respiratory, and sympathetic effects of selective μ and δ opioid agonists microinjected into the hypothalamic nucleus preopticus medialis (POM) of conscious SHR and WKY rats. The μ: receptor agonist D-Ala2-MePhe4-Gly5-ol-enkephalin (DAGO) at a dose of 0.6 or 6.0 nanomoles (Nmol) increased the blood pressure and heart rate in WKY rats. In SHR rats, the lower dose of DAGO similarly had a pressor effect whereas the higher dose was depressor; heart rate was increased only by the 6.0 nmol dose in these animals. In both SHR and WKY rats, this opioid caused respiratory acidosis and elevation of plasma norepinephrine (NE) and epinephrine (E); plasma vasopressin was reduced by the higher dose of DAGO. All of these effects of the μ agonist were reversed by the opiate receptor antagonist naloxone (0.5 mg/kg, i.a.). The 8 opiatereceptor agonist D-Ala2-D-leu5-eukephalin at a dose of 6.0 or 20.0 nmol increased blood pressure and heart rate in both SHR and WKY rats without affecting respiratory variables. Plasma NE and EPI were elevated at the peak of the pressor period.These studies suggest that the anteroventral hypothalamic region may be an important site in central autonomic regulation by opioid peptides. The μ-receptor agonist was more potent than the δ agonist in eliciting cardiovascular and respiratory effects and associated sympatho-adrenomedullary activation. SHRs differed from the normotensive strain by their opposite (depressor) response to the higher dose of DAGO, a finding that may indicate a potentially different role of endogenous opioids and μ receptors in central cardiovascular control in the spontaneous hypertensive rat.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

We recently discovered a potent natriuretic factor in cardiac atrial tissue. The present experiments were designed to determine whether hypertension was associated with altered tissue content of this atrial natriuretic factor. Extracts were prepared using fresh atria from spontaneously hypertensive rats of the Okamoto strain and from their Wistar-Kyoto controls. Two groups of anesthetized, normovolemic rats (Sprague-Dawley) were used to measure the renal natriuretic and chloriuretic effect of each type of extract. Results indicate that atrial content of natriuretic factor is reduced in hypertensive rats compared to control animals. We speculate that chronic release of the factor could have depleted atrial stores, and that increased blood levels of atrial natriuretic factor may be involved in the generation and maintenance of hypertension in this model.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

In vitro affinity for vascular 5HT2and alpha receptors was determined for several compounds (spiperone, ketanserin, mianserin, trazodone, mepiprazole, benzoctamine, m-trifluoromethylphenylpiperazine, m-chlorophenylpiperazine, and l-(l-naphthyl)piperazine) known to interact with serotonin receptors. All compounds competitively inhibited 5HT2and alpha receptors with differing degrees of selectivity. Based on these observations, ketanserin, benzoctamine, and 1- naphthyl)piperazine were evaluated as antihypertensive agents in spontaneously hypertensive rats (SHR). Of these compounds, l-(l-naphthyl)piperazine was a highly selective 5HT2receptor antagonist with a ratio of 5HT2to alpha receptor affinity of greater than 2000. The ratio of 5HT2to alpha receptor affinity for ketanserin and benzoctamine was 63 and 16, respectively. However, the order of affinity toward 5HT2receptors was ketanserin > l-(l-naphthyl)piperazine > benzoctamine whereas the order of affinity toward alpha receptors was ketanserin > benzoctamine > l-(l-naphthyl)piperazine. A similar order of potency toward both 5HT2and alpha receptors was found in pithed SHR based on antagonism of the pressor response to serotonin and methoxamine, respectively. In the SHR, maximum blood pressure reduction at a dose of 10 mg/kg i.p. was approximately 65 and 30 mm Hg for ketanserin and benzoctamine, respectively; l-(l-naphthyl)piperazine did not affect blood pressure. Thus, blood pressure reduction more closely paralleled the in vitro and in vivo potency of these agents toward vascular alpha rather than 5HT2receptors. These data support the contention that alpha receptor blockade rather than selective 5HT2receptor blockade is responsible for the antihypertensive activity of “serotonergic antagonists” in the SHR.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Na+, K+-ATPase activity, phosphorylation, and [3H]ouabain binding in sarcolemma isolated from spontaneously hypertensive rat (SHR) hearts were compared to the same parameters in sarcolemma from normotensive rat (WKY) hearts. Sarcolemma prepared from SHR heart contained significantly less ouabain-inhibitable ATPase activity than sarcolemma from WKY heart. No significant differences in sarcolemmal protein content or recovery were noted between the two groups. The numbers of phosphorylation sites and ouabain binding sites were lower for SHR hearts than for WKY hearts. The KDvalues for ouabain binding were the same (0.30 μM) in cardiac sarcolemma of SHR and WKY. The I50values for inhibition by ouabain of Na+, K+-ATPase were also the same for both groups (SHR = 49 μM; WKY = 44 μM). These data suggest that the decrease of cardiac sarcolemmal Na+, K+-ATPase activity in SHR hearts is due to a decrease in the number of active sites.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Previous studies from our laboratory have shown that chronic intracerebroventricular administration of captopril attenuates the development of hypertension in the spontaneously hypertensive rat of the Okamoto strain (SHR) without altering sodium and water balance, plasma renin, or sympathoadrenal activities. To determine whether the depressor effect of intracerebroventricular captopril was associated with an alteration in peripheral vascular reactivity and/or baroreflex sensitivity, vascular reactivity to phenylephrine and vasopressin was assessed in renal, mesenteric, and hindquarter vascular beds using pulsed Doppler flow probes. Captopril was infused into the jugular vein or lateral ventricle of male SHR and Wistar-Kyoto (WKY) rats for 4 weeks (osmotic mini pump, 1.25 μg/0.5 μ/hr). Control SHR or WKY received intracerebroventricular infusions of vehicle. Four weeks of captopril decreased arterial pressure in both SHR and WKY. In response to phenylephrine and vasopressin, SHR and WKY treated with intracerebroventricular captopril showed significantly attenuated increases in arterial pressure and vascular resistance in comparison to either vehicletreated rats or rats receiving intravenous captopril. Reflex decreases in heart rate in response to phenylephrine were also greater in SHR and WKY treated with intracerebroventricular captopril than in the other rat groups. Neither vascular reactivity nor baroreflex sensitivity was altered in rats treated with intravenous captopril. We conclude that the depressor effect of captopril involves a blunting of vascular reactivity to vasoconstrictors and a potentiation of the baroreflex.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Prostaglandin I2, (PGI2, prostacyclin), a potent vasodilator synthesized by the blood vessels, has been postulated to play a role in hypertension. The purpose of our study was to test this hypothesis by monitoring the in vivo production of PGI2 in Dahl salt-sensitive (S) and salt-resistant (R) rats under normal and high sodium intake. The 24-hour urinary excretion of two endogenous metabolites of PGI2, 2,3-dinor-6-oxo-PGF1α, and 2,3-dinor-13,14-dihydro-6,15-dioxo-PGF1αwas measured by combined gas chromatography-mass spectrometry (GC-MS) and used as an index of the total production of PGI2by the animals. The pattern of urinary excretion of these two metabolites in the R and the S rats during the control period indicated that, under normal conditions, early in life the basal production of PGI2was the same in both groups of rats. Following the chronic administration of a high sodium diet (8.1 % sodium chloride, starting at 36 days of age), a significant and sustained increase in the urinary excretion of 2,3-dinor-6-oxo-PGF, a was documented in the R rats (from 37 ± 7 ng/24 hrs at age 35 days to 63 ± 7, 52 ± 4, and 56 ± 10 ng/24 hrs at 50,60, and 80 days, respectively), whereas the urinary levels of this metabolite decreased slightly in the S rats (from 41 ± 7 ng/24 hrs at age 35 days to 25 ± 5, 30 ± 6, and 28 ± 9 ng/24 hrs at 50, 60, and 80 days, respectively). During the same period, the R rats remained normotensive (103 ± 5 mm Hg, systolic pressure) while the arterial pressure of the S rats increased gradually (to 142 ± 8 and 180 ± 19 mm Hg at ages 60 and 80 days, respectively). After the age of 35 days, the urinary levels of 2,3-dinor-13,14-dihydro-6,15-dioxo- PGF1αdecreased sharply and independently of the diet in all groups, suggesting further transformation of this metabolite by co-oxidation, a well-known age-dependent phenomenon.Results of this study indicate that a high sodium intake is associated with a rise in the overall production of PGI2in the salt-resistant but not the salt-sensitive rats. This observation points to the existence of a defect in the production of PGI2in the salt-sensitive animals, a defect that is uncovered by high sodium intake and that may be causally related to the development of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID