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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study tested the hypothesis that interactions of endogenous angiotensin II (AII) with the noradrenergic neuroeffector junction are important in renin-dependent hypertension. In the in situ blood-perfused rat mesentery, in normal rats exogenous AII potentiated mesenteric vascular responses to periarterial (sympathetic) nerve stimulation (PNS) more than vascular responses to exogenous norepinephrine (NE). In 2-kidney-1-clip (2K-1C) rats with renovascular hypertension mesenteric vascular responses to PNS and NE were greater than in sham-operated rats, and renovascular hypertension mimicked the effects of exogenous AII with respect to enhancing responses to PNS more than responses to NE. In 2K-1C rats, but not in sham-operated rats, 1-Sar-8-Ile-AII markedly suppressed vascular responses to PNS, without influencing responses to NE. Finally, 1-Sar-8-Ile-AII attenuated sympathetic nerve stimulation-induced neuronal spillover of NE in 2K-1C rats, but not in sham-operated rats. These data indicate that renovascular hypertension enhances noradrenergic neurotransmission, and that this enhancement is mediated in part by AII-induced facilitation of NE release.
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PMID:Angiotensin II-noradrenergic interactions in renovascular hypertensive rats. 330

We examined the interrelationships between the pressor response to the administration of norepinephrine and arginine vasopressin and baroreflex function in rats with hypertension of two days' duration induced by heminephrectomy and a clip placed on the right renal artery (2-day clipped rats). Mean arterial pressure was higher in the 2-day clipped rats than in heminephrectomized rats without clips (sham-operated rats). The pressor response in the 2-day clipped rats to both agents increased as compared to the sham-operated rats. This hyperresponsiveness was attenuated by administering an angiotensin II antagonist, [1-Sar, 8-Ile] angiotensin II. Baroreflex sensitivity was studied by measuring changes in arterial pressure and pulse interval in response to the injection of phenylephrine. Baroreflex sensitivity was not decreased but markedly increased in the 2-day clipped rats and unaffected by infusing the angiotensin II antagonist. These results provide evidence that 1) in the 2-day clipped rats there are exaggerated pressor responses to vasoconstrictors; 2) the hyperresponsiveness is not causally related to the change of baroreflex sensitivity; and 3) angiotensin II plays a significant role in the increased pressor responses; however, the baroreflex mechanism is not involved in attenuation of the hyperresponsiveness by the angiotensin II antagonist.
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PMID:Role of baroreflex in the pressor response of rats with hypertension developed by renal artery stenosis. 333 54

A potent renin inhibitor, U-71038 (Boc-Pro-Phe-N-MeHis-Leu psi[CHOHCH2]Val-Ile-Amp), was tested for oral effectiveness. Enzyme kinetic studies indicated that U-71038 was a competitive inhibitor of hog renin with an inhibitor constant (Ki) value of 12 nM. Intravenous as well as oral administration of U-71038 to anesthetized, ganglion-blocked rats infused with hog renin elicited dose-related hypotensive responses. Intravenous administration of U-71038 to conscious, sodium-depleted monkeys caused dose-related decreases of blood pressure and plasma renin activity without affecting heart rate. Similarly, the oral administration of U-71038 at 50 mg/kg to conscious, sodium-depleted monkeys elicited a pronounced hypotension and decrease in plasma renin activity that persisted for 5 hours. The hypotensive responses elicited by intravenous and oral administration of U-71038 to hog renin-infused rats and sodium-depleted monkeys were shown to be due entirely to inhibition of the renin-angiotensin system. A comparison of the results obtained after the intravenous administration of U-71038 with the results obtained after the oral administration of U-71038 implied that at least 10% of the orally administered U-71038 must have been absorbed to cause the observed effects in hog renin-infused rats and sodium-depleted monkeys. The studies demonstrated that an inhibitor of renin with a long duration of action and with oral effectiveness is a feasible entity.
Hypertension 1986 Dec
PMID:An orally active inhibitor of renin. 353 93

A detailed study of the coronary arteries of 111 consecutive necropsies at Ile-Ife, Nigeria is reported. Coronary occlusive disease occurred in eight (7.2%) subjects and involved less than 50% of luminal size in five, and greater than 50% of luminal size in three subjects. Previous medical history was available in four of eight subjects and all four had hypertension. All three subjects with greater than 50% luminal occlusion were hypertensive patients and professionals, one was additionally diabetic and a heavy smoker and serum cholesterol (available in one) was 250 mg/ml. The mean age of the subjects with moderate and severe disease was 54 (range 35 to 71) years. Thus coronary occlusive disease among Nigerians occurred in elderly, affluent and hypertensive patients exposed to Western diets and habits.
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PMID:Coronary artery pathology of 111 consecutive Nigerians. 360 41

Inhibition of renin was induced in conscious marmosets with CGP 29 287, Z-Arg-Arg-Pro-Phe-His-Sta-Ile-His-Lys (Boc)-OMe, a renin inhibitor with a prolonged duration of action. In vitro, CGP 29 287 is a potent inhibitor of primate plasma renin (inhibitory concentration, 50%: human = 1 X 10(-9) M; marmoset = 5 X 10(-9) M) and less potent against dog (2 X 10(-7) M) or rat (3 X 10(-5) M) plasma renin. CGP 29 287 is a weak inhibitor of other aspartic proteases such as porcine pepsin or bovine cathepsin D (inhibitory concentration, 50% = 4 X 10(-5) M). In furosemide-treated marmosets, CGP 29 287 lowered blood pressure and inhibited plasma renin activity during intravenous infusion and after intravenous bolus injection. The duration of action after intravenous injection was dose dependent and ranged from 1 hour after 0.1 mg/kg to more than 3 hours after 10 mg/kg. High doses of CGP 29 287 (100 mg/kg) were active after oral administration. In all experiments a close relation between inhibition of plasma renin activity and reduction of blood pressure was found. A maximum hypotensive response to CGP 29 287 was associated with complete inhibition of plasma renin activity, and the recovery of blood pressure was accompanied by recovery of plasma renin activity. The hypotensive effects of CGP 29 287 were smaller in untreated than in furosemide-treated marmosets. CGP 29 287 had no influence on blood pressure in marmosets after bilateral nephrectomy or after pretreatment with a converting enzyme inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Effects of a specific and long-acting renin inhibitor in the marmoset. 392 88

We examined the time course and extent to which central and peripheral mechanisms contribute to the short-term effects of a 500-mg oral dose of alpha-methyldopa on supine mean arterial pressure, cardiac output, and total peripheral resistance, as well as its effects on total urinary excretion of norepinephrine and its metabolites, in five subjects with essential hypertension. Total peripheral resistance was reduced significantly 1 hour after alpha-methyldopa administration and remained so for the ensuing 7 hours of the study (p less than 0.05). A small but significant reduction in mean arterial pressure occurred 7 hours after the dose (p less than 0.05), while cardiac output did not change significantly. Total 24-hour urinary norepinephrine and metabolite excretion was reduced by 8.1 mumol (35% compared with placebo). The relative distribution of urinary norepinephrine metabolites was unaffected by alpha-methyldopa, and the catecholamine metabolites of alpha-methyldopa, alpha-methylnorepinephrine and alpha-methylnormetanephrine did not account for this reduction. Competitive inhibition of methyldopa transport across the blood-brain barrier and into the central nervous system by large oral doses of isoleucine antagonized most of the effect of alpha-methyldopa. The effects on total peripheral resistance were completely abolished, and small, insignificant changes during the 7-hour study were similar to those observed after placebo. Changes in mean arterial pressure were not significant; however, 24-hour total urinary norepinephrine and metabolite excretion increased by 6.1 mumol to 22.7 mumol (24.7 mumol excreted after placebo). Adding benserazide to the alpha/methyldopa-isoleucine dose regimen in an attempt to inhibit any residual, presumably peripheral, effects of alpha-methyldopa caused little, if any, further antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1986 Jan
PMID:Evidence for a predominantly central hypotensive effect of alpha-methyldopa in humans. 394 83

Constriction of the renal artery and controlled reduction of renal perfusion pressure is followed by a prompt increase in systemic renin activity and a concomitant rise in blood pressure in trained, unanesthetized dogs. The elevated blood pressure induced by the renal artery stenosis can be prevented by prior treatment with the nonapeptide Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, which blocks conversion of angiotensin I to angiotensin II. Further, the nonapeptide can restore systemic pressure to normnal in the early phase of renovascular hypertension. These results offer strong evidence that the renin-angiotensin system is responsible for the initiation of hypertension in the unilaterally nephrectomized dog with renal artery constriction.
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PMID:Inhibition of angiotensin conversion in experimental renovascular hypertension. 434 Nov 25

Rabbit brain endo-oligopeptidase B inactivates angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) and angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) by hydrolysis of the Pro7-Phe8 peptide bond. The site of hydrolysis was determined in preparative and analytical experiments in which both products were recovered in a molar ratio of 1:1, and the sum of the products plus unhydrolyzed substrate accounted for the starting material. The enzyme has a Km of 6.3 x 10(-5) M for angiotensin II at pH 8.3 and is activated 30-fold with 4.8 mM dithiothreitol. BPP9a ( less than Gln-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, SQ 20,881) inhibits the inactivation of angiotensin II with an I50 of 5 x 10(-5) M. BPP5a (less than Gln-Lys-Trp-Ala-Pro, SQ 20,475) is less active and D-3-mercapto-2-methylpropanoyl-L-proline (captopril, SQ 14,225) has essentially no activity. These endo-oligopeptidase B in angiotensin I and II metabolism remains to be established.
Hypertension
PMID:Brain endo-oligopeptidase B: a post-proline cleaving enzyme that inactivates angiotensin I and II. 617 71

A prospective study of congestive cardiac failure in 221 elderly Nigerians seen at Ahmadu Bello University Hospital, Zaria, and Ife University Teaching Hospitals Complex, Ile-Ife from 1974 to 1979 is reported. Hypertension, iodopathic cardiomegaly and pulmonary heart disease were major causes of cardiac failure. No case of coronary atherosclerotic heart disease was seen. Ventricular conduction defect was the commonest E.C.G. abnormality recorded. In over half of the patients, there was coexisting disease, mild to moderate anaemia being the most common.
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PMID:Congestive cardiac failure in elderly Nigerians: a prospective clinical study. 645 36

Two angiotensin II analogues (AIIA), 1-sarcosine, 8-isoleucine angiotensin II ([Sar, Ile]-AII) and 1-sarcosine, 8-alanine angiotensin II ([Sar, Ala]-AII), were infused in six normal volunteers on high, regular and low sodium diets. The agonist and antagonist activities of these AIIA on blood pressure (BP), plasma aldosterone concentration (PAC), creatinine clearance and plasma renin activity were examined. Both AIIA had agonistic pressor activities in subjects on high and regular sodium diets, [Sar, Ile]-AII being more potent than [Sar, Ala]-AII. Both AIIA caused similar elevation of PAC in subjects on high and regular sodium diets, and an equally fall in PAC in subjects on a low sodium diet. Both AIIA strongly antagonized the rise in BP, the increase in PAC and the reduction of Ccr induced by AII administration in subjects on all three sodium diets. The results indicate that both AIIA can be used to examine the activity of the renin-angiotensin system in patients with hypertension, and they also suggest that AII interaction with its receptors differs in different target tissues.
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PMID:Effects of two angiotensin II analogues on blood pressure, plasma aldosterone concentration, plasma renin activity and creatinine clearance in normal subjects on different sodium intakes. 700 66


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