Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin-converting enzyme activity of the aortic subcellular fractions (homogenate, mitochondria, microsomes and supernatant) was determined in normotensive and experimental hypertensive rats (1-clip, 1-kidney Goldblatt hypertensive; 1-clip, 2-kidney Goldblatt hypertensive and 2-clip, 2-kidney hypertensive rats). The systolic blood pressure markedly elevated in each group of experimental hypertensive rats, while it did not in normotensive rats. Angiotensin-converting enzyme activity was consistently high in the microsomal and supernatant fractions of the aorta in experimental hypertensive rats as well as in normotensive rats. However, the enzyme activity from each fraction of the aorta in 1-clip, 2-kidney Goldblatt hypertensive rats was significantly higher than that in normotensive and other experimental hypertensive rats. There was no significant difference in the enzyme activity among normotensive, 1-clip, 1-kidney Goldblatt hypertensive and 2-clip, 2-kidney hypertensive rats. The angiotensin-converting enzyme, widely distributed in subcellular fractions of the aorta, may play a possible role in the local control of vascular tone. It seems likely that increased angiotensin-converting enzyme activity in arterial tissue contributes to the initiation or development of hypertension in 1-clip, 2-kidney Goldblatt hypertension in rats.
 ...
PMID:[Angiotensin-converting enzyme activity of the aorta in experimental hypertensive rats]. 630 98

Experiments were performed to determine if the activation of the renin-angiotensin system that occurs during the development of two-kidney, one clip Goldblatt hypertension in dogs is accompanied by increases in vasopressin and adrenocorticotrophic hormone (ACTH) secretion. Following renal artery constriction, there were marked increases in arterial blood pressure, plasma renin activity (PRA), and plasma angiotensin II (AII) concentration. These changes were accompanied by an increase in plasma vasopressin concentration during the second week following constriction, and there were significant correlations between plasma vasopressin concentration and PRA (r = 0.57, p less than 0.001), and between plasma vasopressin concentration and plasma AII concentration (r = 0.59, p less than 0.001). In contrast, plasma corticosteroid concentration, used as an index of changes in ACTH secretion, did not change significantly. Acute blockade of the renin-angiotensin system with captopril or saralasin produced the expected changes in blood pressure, PRA, and plasma AII concentration but did not decrease plasma vasopressin or corticosteroid concentrations. These results indicate that during the development of renal hypertension in dogs, there may be an interaction between the renin-angiotensin system and vasopressin, but not between the renin-angiotensin system and the pituitary-adrenal axis. They also show that the antihypertensive action of captopril in this experimental model is not mediated via suppression of vasopressin, ACTH, or corticosteroid secretion.
Hypertension
PMID:Role of the renin-angiotensin system in the control of vasopressin and ACTH secretion during the development of renal hypertension in dogs. 631 79

Two-kidney, one clip Goldblatt hypertension of 2, 4 and 8 weeks duration was induced in 100-g male Wistar-Kyoto rats. Nucleic acid content was determined in the isolated cardiac muscle cells from the left ventricle. The profile for several major proteolytic activities in either isolated cardiac muscle cells or left ventricle preparations was also studied, using [3H]acetyl-casein as substrate. From the soluble fraction of the tissue or cell preparation, a pH 6 proteolytic activity, two forms of calcium-activated protease as well as cathepsin D were identifiable by inhibitor assay or DEAE-cellulose chromatography. From the myofibrillar fraction of the same preparation, two kinds of proteolytic activity were detected at alkaline pH: a phenylmethylsulfonyl fluoride (PMSF) inhibitable activity that was serine protease-like and the other a N-ethylmaleimide (NEM) inhibitable activity that resembled Ca2+-activated protease. At 2 weeks of hypertension, there was a significant increase in the pH 6 proteolytic activity as well as the calcium-activated protease I and the NEM-inhibitable alkaline protease activities, while the other identifiable proteolytic activities remained unchanged. Lysosomal cathepsin D showed a rise in activity only after 8 weeks of hypertension. These results may be related to the development of myocyte necrosis and lysis that occur in this model of hypertensive cardiomyopathy.
 ...
PMID:Proteolytic activities in hypertensive cardiomyopathy of rats. 634 96

Efferent renal innervation is composed of postganglionic sympathetic fibers to the renal arterioles, juxtaglomerular apparatus, and renal tubules. Increased efferent renal sympathetic nerve activity results in increased renal vascular resistance, renin release, and sodium retention. These responses from enhanced renal sympathetic activity contribute to normal cardiovascular homeostasis but could also facilitate the development of hypertension by shifting the arterial pressure-renal sodium excretion curve to the right. Accordingly, interruption of the renal nerves should prevent the development of hypertension in animal models in which increased sympathetic nervous system activity has been implicated. Renal denervation delays the development of hypertension and results in greater sodium excretion in the Okamoto and New Zealand spontaneously hypertensive rat and in the DOCA-salt-treated rat, suggesting that these responses are due, at least in part, to loss of efferent renal nerve activity. Similar sympathetically mediated renal vasoconstriction has been implicated in the pathogenesis of early essential hypertension in man. Recent studies indicate that the kidney is a sensory organ with mechano-receptive and chemoreceptive afferent renal nerves involved in renorenal and cardiovascular regulation. Renal denervation in established one-kidney one-clip and two-kidney one-clip Goldblatt hypertension in the rat and chronic coarctation in the dog results in an attenuation of the hypertension. The depressor effect of renal denervation in these models is not due to change in renin activity or sodium excretion but is associated with decreased activity of the sympathetic nervous system. These findings suggest that the afferent renal nerves contribute to the pathogenesis of renovascular hypertension by enhancing the activity of the sympathetic nervous system. The role of the afferent renal nerves in renovascular hypertension in humans warrants further study.
 ...
PMID:Renal nerves in the pathogenesis of hypertension in experimental animals and humans. 634 99

Because of previous suggestions of impaired renal blood flow in the contralateral kidney of Goldblatt hypertensive animals, we examined the maximal vasodilator capacity of the contralateral kidney in 13 instrumented dogs during progression of Goldblatt hypertension. Constriction of a single renal artery (RAC) followed a week or more later by total renal artery occlusion (RAO) increased mean arterial blood pressure (BP) from a control level of 102 +/- 3 to 135 +/- 7 mmHg (P less than 0.001) and increased plasma renin activity (PRA) from 0.69 +/- 0.16 to 10.2 +/- 3.9 ng angiotensin I X ml-1 X h-1 (P less than 0.05) at 2 wk after RAO. The hypertension was accompanied by an increase in basal renal blood flow (RBF) from 224 +/- 21 to 300 +/- 27 ml/min (P less than 0.01) and RBF at maximal vasodilatation from 505 +/- 24 to 673 +/- 52 ml/min (P less than 0.05). Hypertension and the increase in PRA waned, but BP remained higher than control at 4 wk after RAO (117 +/- 6 mmHg, P less than 0.005). Basal and maximal RBF were sustained at the higher levels throughout the 4-wk period after RAO. When RBF was expressed on a per gram basis, basal and maximal flow before (3.72 +/- 0.40 and 8.26 +/- 0.62 ml X min-1 X g-1, respectively) did not differ from that in the final experiment after RAO (3.85 +/- 0.34 and 8.19 +/- 0.78 ml X min-1 X g-1). The basal and minimal vascular resistances based on flow per gram were increased by 24 +/- 8 and 41 +/- 16% (P less than 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Vasodilator capacity of contralateral kidney in Goldblatt hypertensive dog. 635 40

One-kidney, one clip (1K1C) and two-kidney, one clip (2K1C) Goldblatt hypertension was produced in rats by placing 0.30, 0.25, or 0.20 mm silver clips on the left renal artery. Mean arterial pressure (MAP) and plasma renin activity (PRA) were measured in conscious rats 24 to 28 days after clipping. The MAP in control rats (n = 38) was 116 +/- 1 mm Hg (mean +/- SEM). The 0.30, 0.25, and 0.20 mm clips produced MAPs of 133 +/- 2, 161 +/- 5, and 189 +/- 5 mm Hg, respectively, in 1K1C rats, and 123 +/- 2, 129 +/- 3, and 172 +/- 5 mm Hg in 2K1C rats (n = 17-20). When 1K1C and 2K1C groups were compared, MAP was significantly greater in 1K1C rats at all clip sizes. No treatment group's PRA was different than control (4.8 +/- 0.4 ng AI/ml/hr), except for the 0.20 mm 2K1C rats (16.2 +/- 3.1 ng AI/ml/hr). Renal artery pressure (RAP) was measured in another series of experiments and was not different from control in all but the 0.20 mm 1K1C rats. With identical clip sizes, 2K1C rats showed smaller pressure gradients than 1K1C across the clips: 0.30 mm, 8.5 +/- 1.7 vs 10.7 +/- 1.9 mm Hg; 0.25 mm, 16.5 +/- 1.2 vs 42.1 +/- 7.5 mm Hg; 0.20 mm, 51 +/- 5.3 vs 79.1 +/- 5.7 mm Hg (n = 8-12). Therefore, both the increase in MAP and the pressure gradient across the clip were greater in the 1K1C rats at every clip size.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Effects of graded renal artery constriction on blood pressure, renal artery pressure, and plasma renin activity in Goldblatt hypertension. 636 82

An anterior hypothalamic knife cut that leaves intact two central sites of action of angiotension II produces the same deficits in the pressor responses to angiotensin II that have been attributed to destruction of two circumventricular organs (the subfornical organ and the organum vasculosum of the lamina terminalis). The central pressor actions of angiotensin II are necessary for the full expression of renin-dependent renal hypertension. The anterior hypothalamic knife cut attenuates renin-dependent aortic ligation hypertension. It has been shown that electrolytic destruction more anterior to this knife cut, in the anteroventral 3rd ventricle region, also attenuates two forms of renin-dependent hypertension, aortic ligation hypertension and two-kidney Goldblatt hypertension in the rat. Electrolytic lesions in the subfornical organ also reduce renin-dependent, two-kidney Goldblatt hypertension. These data are consistent with the hypothesis that a common efferent system from the organum vasculosum of the lamina terminalis and subfornical organ mediates the central pressor response to angiotensin II and is involved in the development of renin-dependent hypertension. A model is proposed for the circuitry in the rat forebrain that is involved in the pressor response to angiotensin II.
 ...
PMID:The angiotensin II pressor system of the rat forebrain. 637 Apr 91

Reversal of early Goldblatt two-kidney, one-clip hypertension is associated with a fall in plasma renin. To define the role of this in blood pressure normalization we maintained preoperative hypertension for 12 h after unclipping or removal of the ischemic kidney, by angiotensin II or norepinephrine infusions during continuous blood pressure monitoring. High infusion rates of angiotensin II (1 microgram X kg-1 X min-1) were needed to reproduce hypertensive pressures. On stopping angiotensin II there was a rapid initial fall in blood pressure but not to normal (176 +/- 3.1 to 138 +/- 4.3 mmHg at 1 h), and a later slower fall to normal by 24 h (114 +/- 3.9). This response was identical to that of dextrose-infused animals (180 +/- 8.2 to 146 +/- 7.0 at 1 h and 113 +/- 5.6 at 24 h), apart from a transient rise in blood pressure associated with hyperreninemia in unclipped animals 12 h postinfusion. In contrast, after norepinephrine blood pressure fell immediately to normal. Similar responses were seen in normal rats after 12-h pressor infusions of angiotensin II or norepinephrine. These results show that the fast and slow components of the blood pressure fall following reversal of Goldblatt hypertension are delayed but otherwise unaltered specifically by angiotensin II. The need for pharmacologic doses, however, suggests that mechanisms in addition to the direct vasopressor action of angiotensin II are involved.
 ...
PMID:Delayed reversal of Goldblatt hypertension by angiotensin II infusion in the rat. 637 14

This study examines the role of the renal nerves in the chronic and early developmental stages of one-kidney, one-clip (1K-1C) Goldblatt hypertension. Groups of uninephrectomized Sprague-Dawley rats underwent renal artery constriction with a clip of an internal diameter of 0.23 mm (groups 1 and 3) or 0.40 mm (groups 2 and 4) to produce severe or moderate hypertension. Two weeks later, groups 1 and 2 were subjected to renal denervation and groups 3 and 4 were denervated 6 and 7 wk after clipping, respectively. In all four groups, hypertension remained unchanged during the subsequent 2 wk after denervation. To study further the effects of renal denervation during the early onset of hypertension, groups 5, 6, and 7 received the smaller (0.23 mm) clip after uninephrectomy. Groups 5 and 6 were renal denervated immediately before clipping; group 7 was not denervated. In groups 6 and 7 the renin-angiotensin system was blocked with a continuous infusion of the converting-enzyme inhibitor captopril for 24 h before and 15 days after clipping. In group 5, renal denervation did not prevent a prompt and severe rise in the systolic blood pressure. In groups 6 and 7, infusion of captopril prevented the hypertension only during the first 4 days after clipping; at no time was there a difference in the systolic blood pressure curves of groups 6 and 7 during or after captopril infusion. These data demonstrate that regardless of the severity and duration of hypertension, renal denervation failed to attenuate either the development or the maintenance of 1K-1C Goldblatt hypertension in the rat. Thus the present results fail to provide support for the concept that the renal nerves modulate the hypertension in this experimental model.
 ...
PMID:Pathogenesis of one-kidney, one-clip hypertension in rats after renal denervation. 637 27

Studies from our laboratory suggest that the afferent renal nerves from the clipped kidney enhance sympathetic nervous system activity in established one-kidney, one clip and two-kidney, one clip Goldblatt hypertension. Because adenosine is released during renal ischaemia and adenosine has been shown to increase the frequency of afferent renal nerve signals, we proposed the hypothesis that intrarenal adenosine might produce hypertension by activating the sympathetic nervous system via the afferent renal nerves. To examine this hypothesis, changes in arterial pressure and activity of the sympathetic nervous system were measured during renal artery infusion of adenosine before and after renal denervation in uninephrectomized sodium replete conscious dogs. Intrarenal adenosine infusion produced a 21 +/- 3 mmHg mean arterial pressure rise in association with an increase in plasma norepinephrine. Ganglionic blockade during intrarenal adenosine infusion resulted in a significantly greater decrease in arterial pressure compared to control responses. After renal denervation, intrarenal adenosine infusion resulted in no change in arterial pressure, plasma norepinephrine or arterial pressure response to ganglionic blockade. To further assess sympathetic activity changes, right renal norepinephrine secretion and multifibre efferent neural traffic were measured during left renal artery adenosine infusion in alpha-chloralose-anaesthetized dogs. Left renal artery adenosine infusion resulted in increased right renal vascular resistance in association with increased renal norepinephrine secretion and increased efferent neural activity. The data indicate that in the dog with intact renal nerves, intrarenal adenosine produces hypertension by activating the sympathetic nervous system.
 ...
PMID:Intrarenal adenosine produces hypertension by activating the sympathetic nervous system via the renal nerves in the dog. 639 33


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>