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

Investigations were performed on components of the renin-angiotensin system (RAS) in homogenate extracts of vascular tissue and aortic smooth muscle cells cultivated in vitro. Determinations of isoelectric points and pH optima indicated the existence in aortic homogenate extracts of two local angiotensin I (AI)-forming enzymes (AIFE) that were different from those of plasma, renal cortex, veins, and aortic smooth muscle cells. The pH optima for AI-converting enzyme (ACE) from vascular tissues, aortic smooth muscle cells, and plasma were in the same range (pH 8.0-8.5), and in agreement with those measured previously in other tissues. In contrast, in vitro studies with the ACE inhibitors MK-421 and MK-422 and measurement of isoelectric points suggested that aortic ACE was different from the plasma enzyme. AIFE and ACE activities were found to be elevated in spontaneously hypertensive rats (SHR). The biochemical characteristics of the enzymes investigated in the vascular tissue of SHR were not different from those of the normotensive controls. AI- and AII-degrading enzymes were found both in aortic tissue and in aortic smooth muscle cells. One potent AI-degrading enzyme different from ACE was observed in aortic tissue. A high ratio of AI/AII immunoreactivities in arterial walls suggests the availability of renin substrate, and that AI-degrading enzymes are the rate-limiting enzymes for AII formation. The results further support the concept of an intrinsic vascular RAS.
Hypertension
PMID:Investigations of components of the renin-angiotensin system in rat vascular tissue. 632 51

The levels of norepinephrine (NE), epinephrine (E), and angiotensin II immunoreactivity (AIIir) in plasma and in cerebrospinal fluid (CSF) were measured in eight conscious dogs before and during a 28-day period in the development of two-kidney, one clip (2K1C) hypertension produced by a two-step procedure. The early phase (less than 7 days) of hypertension following partial constriction of the renal artery was accompanied by tachycardia and increases in concentrations of NE and AIIir in both plasma and CSF; E did not change. One week later blood pressure remained elevated (107 +/- 2 after vs 88 +/- 2 mm Hg before clipping, p less than 0.05), but other variables returned to control values. Occlusion of the partially constricted renal artery caused severe hypertension that was initially associated with a transient decrease in levels of NE in both plasma and CSF and a sustained rise in plasma and CSF concentrations of AIIir that persisted for as long as 2 weeks after the second operation. None of these effects was seen in nine sham-operated dogs. Since activation of the renal pressor system is associated with time-related changes in the concentrations of NE and AII in both plasma and CSF, these observations indicate early involvement of both sympathetic and renin-angiotensin systems in the pathogenesis of renovascular hypertension.
Hypertension
PMID:Alterations in plasma and cerebrospinal fluid norepinephrine and angiotensin II during the development of renal hypertension in conscious dogs. 633 56

The renal hemodynamic response to subpressor doses of angiotensin II (AII; 0.1 and 0.5 ng/min/kg) was investigated in untreated 49-year-old men (n = 50) representing a wide blood pressure range. Renal blood flow, renal vascular resistance (RVR), glomerular filtration rate (GFR), filtration fraction (FF), plasma renin activity (PRA), plasma AII, plasma aldosterone, and the urinary excretion of sodium and norepinephrine were studied. The higher the initial blood pressure the greater was the increase in RVR in response to AII infusion (p less than 0.002), indicating an increased renal vascular reactivity with increase in initial blood pressure. The AII infusion gave a significant rise in RVR in both the borderline and hypertensive group, but gave no increase in RVR in the normotensive group, implying an enhanced sensitivity of the renal vasculature in the borderline and hypertensive group. The increase in RVR was greater in the hypertensive than in the borderline group, i.e., the hypertensives had a steeper dose-response curve than the borderline group, which points to the presence of structural vascular changes in the renal vessels in the hypertensives. The increase in RVR in response to AII was positively correlated to sodium intake and plasma aldosterone concentration, indicating that these two factors might modulate the renal vascular reactivity. These factors could, however, only partly explain that RVR increased more the higher the initial blood pressure. Thus, the results indicate that there is an increased reactivity of the renal vascular bed to AII in essential hypertension. The increased reactivity seems to be mediated through an increased sensitivity of the renal vasculature to AII in mild essential hypertension and also through the presence of structural vascular changes in established hypertension. These factors may lead to a reduced excretion of sodium and water and may therefore be of importance in the development and progression of essential hypertension.
Hypertension
PMID:Effects of subpressor doses of angiotensin II on renal hemodynamics in relation to blood pressure. 634 Dec 20

Conscious pregnant and nonpregnant rabbits were used to further evaluate the role of prostaglandin (PG) and plasma renin activity (PRA) in the systemic hemodynamics of pregnancy. Pregnant rabbits had high peripheral blood levels of both PGE2 and PRA. Systemic blood pressure was not affected in either pregnant or nonpregnant by the administration of an inhibitor of prostaglandin synthesis. Pregnant rabbits, however, had a much larger decrease in blood pressure than nonpregnant animals when given the angiotensin I (AI)-converting-enzyme inhibitor, captopril. Pregnant rabbits were more resistant to the pressor effect of exogenous AII than nonpregnant animals. The pressor effect of AII increased in pregnant rabbits after the administration of meclofenamate and parturition but was not changed by volume expansion. In contrast, the sensitivity of nonpregnant rabbits to AII increased after volume expansion, but not after treatment with inhibitors of prostaglandin synthesis. These studies demonstrate that a remarkable similarity exists between pregnant rabbits and pregnant women in the pressor response to AII. This study is the first to correlate the vasopressor response to AII with PRA and the level of a circulating vasopressor prostaglandin in pregnant animals. The results strongly suggest that this model will be fruitful in further attempts to define the factors controlling systemic hemodynamics during pregnancy.
Hypertension
PMID:The conscious instrumented rabbit: a model for the study of mechanisms of blood pressure regulation during pregnancy. 634 60

Evidence for an intracellular pathway for angiotensin synthesis in the central nervous system (CNS) was examined using immunohistochemistry to compare the distribution of angiotensin I (AI), AII, angiotensinogen, and renin in the hypothalamic paraventricular nuclei (PVN) and supraoptic nuclei (SON), median eminence (ME), and pituitary gland in intact and nephrectomized rats. In intact rats injected intracerebroventricularly (i.c.v.) with colchicine, AII neurons were found in the parvocellular PVN, and terminals were seen in the external lamina of the ME. In the pituitary gland, AII was localized within cells of the anterior and intermediate lobes, whereas the posterior pituitary was unstained. In contrast, 24 to 48 hours following nephrectomy, AII-labeled neurons were observed in the magnocellular PVN and SON, even without the aid of i.c.v. colchicine. Likewise, axons within the internal layer of the ME were now labeled, but the pituitary was completely devoid of staining except for the intermediate lobe. AI-labeled neurons were observed only in the parvocellular PVN. Angiotensinogen was localized in the mediobasal hypothalamus, but the PVN and SON were not labeled. Immunoreactive renin was localized within the magnocellular PVN, SON, and posterior lobe of the pituitary in nephrectomized and intact animals. Because of the close overlap of AI and AII staining, these results suggest that AI and AII could represent a precursor product relationship in the CNS. In contrast, in the intact animals, renin and angiotensinogen do not appear to be associated with AII. However, a possible relationship between AII and renin may exist in the magnocellular PVN and SON, since labeled neurons were seen in these nuclei following nephrectomy.
Hypertension
PMID:Distribution of immunoreactive angiotensin II, angiotensin I, angiotensinogen and renin in the central nervous system of intact and nephrectomized rats. 637 93

By inhibiting ACE, captopril blocks the conversion of AI or AII and augments the effects of bradykinin both in vitro and in vivo. In rats, dogs, and monkeys with 2-kidney renal hypertension, orally administered captopril rapidly and markedly reduces blood pressure; this antihypertensive effect apparently occurs via a renin-dependent mechanism; that is, the inhibition of ACE. In 1-kidney renal hypertension studies in rats and dogs, it was determined that oral doses of captopril markedly lowered blood pressure, but only after several days of dosing; the mechanism is thought to be non-renin dependent. In SHR, daily oral doses of captopril progressively lowered blood pressure; normal levels were attained by the sixth month. In all species studied, the reduction in blood pressure resulted from a reduction in total peripheral resistance; cardiac output remained unchanged or increased. In humans, captopril reduces blood pressure in patients with essential hypertension with low, normal, and high renin levels, and in patients with renovascular hypertension and hypertension associated with chronic renal failure. In hypertensive patients with high plasma renin activity, captopril apparently exerts most of its pharmacologic effects through inhibition of ACE. The means by which captopril reduces high blood pressure associated with low or normal PRA is not known, but it is clear that captopril does not act on an overactive plasma renin-angiotensin system in these cases. The antihypertensive effect of captopril is enhanced when it is given in combination with a diuretic or after salt depletion. Captopril was rapidly and well absorbed in all species tested, including man. Studies in rodents indicated that ingestion of food caused a reduction in the extent of absorption and bioavailability of captopril. Captopril and/or its metabolites were distributed extensively and rapidly throughout most tissues of normal rats; no radioactivity was detected in the brain. In vitro and in vivo, captopril formed disulfide bonds with albumin and other proteins. This binding was reversible in nature. In vitro studies in blood indicates that the disulfide dimer of captopril and mixed disulfides of captopril with L-cysteine and glutathione were formed. In intact blood cells, captopril remained in the reduced form (sulfhydryl), whereas in whole blood or plasma, captopril was converted to its disulfide dimer and other oxidative products. Biotransformation of captopril may involve both enzymatic and nonenzymatic processes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Captopril: pharmacology, metabolism and disposition. 643 80

To better define the intrarenal hemodynamic effects of angiotensin in human renovascular hypertension, 10 patients underwent renal hemodynamic and functional measurements before and during infusion of a competitive angiotensin analog, [Sar1, Thr8] AII. Eight had technically satisfactory split function studies. Despite a fall in mean arterial pressure (132 +/- 6 to 121 +/- 6 mm Hg, p less than 0.05) and humoral changes consistent with angiotensin-mediated hypertension, the intrarenal effects of this analog were commonly those of an angiotensin agonist, producing vasoconstriction and sodium retention. This was quantitatively greatest in the contralateral kidney, whose preinfusion sodium excretion (86 +/- 30 microEq/min vs 25 +/- 9 microEq/min, p less than 0.02) and glomerular filtration rate (76 +/- 7 ml/min vs 41 +/- 7 ml/min, p less than 0.01) were higher than the stenotic kidney. In some cases, an increase in renal blood flow and rise in sodium excretion were evident during angiotensin blockade, suggesting a tonic intrarenal action of angiotensin. Although renin vein renin values differed markedly between the stenotic and contralateral kidney (ratio = 2.05 +/- 0.30), relative changes in effective renal plasma flow were correlated (r = 0.84: p less than 0.01) during infusion of this analog. These results underscore the differences in sensitivities between vascular beds to the effects of angiotensin II and the major role of the contralateral kidney in renal function and sodium homeostasis in human renovascular hypertension.
Hypertension
PMID:Responses of the stenosed and contralateral kidneys to [Sar1, Thr8] AII in human renovascular hypertension. 661 41

The non-cleared influences of the sympathetic nervous system [sN] on structural reactions of SHR and on the direct cardiac effects of AII and the structural vascular behavior were investigated. In 67 spontaneously hypertensive rats (Okamoto-Aoki) and 55 normotonic Wistar rats (NR) the blood pressure behaviour, the structural vascular and organ reactions and the noradrenaline (NA) content of the myocardium were examined with an intact sympathetic nervous system as well as after its almost complete elimination by chemical sympathectomy with 6-hydroxy-dopamine (6-OH-DA). Moreover, the functional and structural responsiveness of the arterial vessels of sympathectomized animals to angiotensin II administrations was investigated. 6-OH-DA in the dosage applied, induces during its time of action in NR a smaller, in SHR a larger decrease of blood pressure and, presumably induced by intense NA-depletion of the myocardium, myocardial alterations. Despite extensive AII-induced alterations of the already early hypertrophically-hyperplastically changed vascular wall, the structural and functional responsiveness of the arterial vascular system was maintained even after sympathectomy, and the sensitivity of the SHR to AII remained. For maintaining hypertension, the cooperation of structural and functional influences is necessary, as is indicated by the reduction of blood pressure in sympathectomized SHR and its regular return to the daily initial values of normotonic animals under additional AII administration. Besides the vascular alterations contributing to the exacerbation of the hypertension, here the sNS is of essential importance. For obtaining a total pressure effect of AII the sNS obviously has not necessarily to be intact, though its activity state can influence the responsiveness of the arterial vascular system to AII. The reduction of the sympathicotonus by sympathectomy seems to have a protective effect on the development of AII-induced structural vascular alterations; in contrast to the myocardium in SHR, in which it induces an exacerbation and an increase in the AII-induced myocardial alteration. These findings obtained from rats are supposed to be important also for the essential hypertension in man. By maintaining the functional responsiveness of the arterial vascular system, antihypertensives which react with the different parts of the sNS cab become effective while structural alterations of the vascular wall can be influenced, too. The possibility of the simultaneous development of myocardial alterations should be taken into special consideration.
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PMID:[Functional and structural behavior of the cardiovascular system of normotonic and spontaneously hypertensive rats following chemical sympathectomy and angiotensin administration]. 680 96

1. Two-kidney one-clip hypertension was produced in rats by application of a 0.20 mm clip to the left renal artery. 2. After three weeks, the animals had mildly elevated PRA, kidney renin was elevated in the clipped kidney and markedly suppressed in the contralateral kidney when compared to values in sham-operated rats. 3. Intrarenal AII was elevated in the clipped kidney either when compared to the contralateral kidney or to values in the controls. However, in the contralateral kidney, AII was not different from controls. 4. Changes in intrarenal AII do not, therefore, always parallel those of renal renin. Failure of suppression of AII in the contralateral kidney is likely to be of pathogenetic importance in development of hypertension in this experimental model.
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PMID:Failure of suppression of intrarenal angiotensin II in the contralateral kidney of one-clip two-kidney hypertensive rats. 699 Nov 77

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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