Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This case report describes a patient with malignant hypertension and phaeochromocytoma in whom blockade of angiotensin II receptors by the competitive antagonist 1-sar-8-ala-angiotensin II (Saralasin) resulted in a partial correction of the elevated BP. Plasma renin activity was high and rose further during the blockade. Competitive inhibition of angiotensin II by Saralasin does not abolish the pressor effect of catecholamines. It was therefore interesting to observe that in this patient with phaeochromocytoma, independently, both alpha-adrenergic receptor blockade and angiotensin II receptor blockade were effective in lowering BP.
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PMID:Partial correction of hypertension by angiotensin II blockade in a patient with phaeochromocytoma. 1 5

When studied on isolated rat mesenteric arteries perfused with Tyrode's solution, angiotensin I and angiotensin II (1 ng/ml), a synthetic tetradecapeptide renin substrate, and a purified hog renin substance (50-100 ng/ml) potentiated vasoconstrictor responses to sympathetic nerve stimulation and to injected norepinephrine without altering basal pressure. These agents produced a greater augmentation of the vasoconstrictor responses to nerve stimulation than to injected norepinephrine. The potentiation of vasoconstrictor responses to sympathetic nerve stimulation and injected norepinephrine which was elicited by renin substrate and angiotensin I was abolished by an inhibitor of angiotensin I-converting enzyme, SQ 20,881, and by an angiotensin II receptor antagonist, [Sar1-Ile8]angiotensin II. In contrast, the potentiating effect of angiotensin II was blocked only by the latter compound. We conclude that utilization of renin substrate within the vascular wall by renin or renin-like enzymes results in the formation of angiotensin I, which is converted to angiotensin II. Angiotensin in turn potentiates the vasoconstrictor responses to adrenergic stimuli presumably by augmenting release of the adrenergic transmitter and inhibiting its neuronal reuptake as well as by increasing vascular reactivity to norepinephrine.
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PMID:Facilitation of adrenergic transmission by locally generated angiotensin II in rat mesenteric arteries. 17 59

The renin angiotensin system has an important role in regulating arterial blood pressure in homeostasis and disease. A reciprocal relationship exists between sodium balance and the circulating levels of renin and angiotensin II. The vascular responsiveness to angiotensin II, the major vasconstrictor component of the renal pressor system, can be impaired by numerous factors including sodium depletion or a reduction in effective plasma volume. In situations in which the renin-angiotensin system is activated, a negative relationship between the angiotensin II pressor response and the circulating angiotensin II level is observed. This effect seems to involve a change of the angiotensin II receptor interaction in the vascular smooth muscle. The prevention of angiotensin II generation by the inhibition of converting enzyme causes an immediate increase in the pressor response to angiotensin; after bilateral nephrectomy, it takes much longer to develop. In addition, the depressor response to angiotensin antagnoists and converting enzyme inhibitor is preserved after bilateral nephrectomy for much longer periods than can be accounted for by the disappearance of circulating renin. These observations support the view that the decrease in vascular response to angiotensin II during sodium deprivation or when body fluid volumes are reduced is the result of prior occupancy of the receptor sites by endogenous hormone generated both in the plasma and locally within blood vessel walls. Therefore, a change in the number or affinity of receptors consequent to a change in sodium balance or as a modulating function of the renin-angiotensin system need not be postulated to explain changes in angiotensin vascular responsiveness.
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PMID:Vascular angiotensin receptors and their role in blood pressure control. 18 2

Saralasin, 10 microgram/kg per min, caused an immediate rise in blood pressure in 52 of 57 (91.2%) hypertensive patients. The increase in diastolic pressure averaged 18.8 +/- 1.83 mm Hg (mean +/- SE) in normal renin patients on a normal salt intake. This immediate pressor response was absent in only five high renin patients and, conversely, was very large in three low renin patients. Direct arterial recordings are necessary to define the response accurately; it begins in 60--90 seconds, peaks in amplitude at 2.05 +/- 0.38 minutes, and subsides over the next 5 minutes in normal renin and high renin patients. The blood pressure elevation is inversely related to background plasma renin activity (r = -0.66, P less than 0.001), and also is directly, but weakly, related to 24-hour urinary sodium excretion (r = + 0.29). Therefore, the amplitude of the elevation is predictably diminished by the rise in plasma renin consequent to prior sodium restriction, and also by preliminary receptor exposure to low dose nonpressor infusions of saralasin itself (0.01-0.1 microgram/kg per min). Phentolamine had no effect on the response in two patients. We propose that the immediate pressor response to saralasin is related directly to the preexisting degree of vacancy of angiotensin II vascular receptors and that the initial agonistic action of the drug may prove useful in defining the angiotensin II receptor status in hypertensive diseases.
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PMID:The immediate pressor response to saralasin in man: a test of angiotensin II receptor vacancy. 21 54

The binding affinity and concentration of specific angiotensin II receptor sites of rat adrenal cortical cells and homogenates were determined after 1 and 6 wk of altered sodium and potassium intake. Sodium deprivation caused marked increases in plasma renin, blood angiotensin II, and plasma aldosterone, and was accompanied by a significant increase (+74%) in the number of specific angiotensin II receptor sites per adrenal cortical cell. High potassium intake was followed by increased serum potassium and markedly elevated plasma aldosterone, with subnormal levels of renin and angiotensin II and a 170% increase in the number of angiotensin II receptors per cell after 1 wk. Sodium loading and potassium deprivation were followed by the opposite effect upon adrenal receptors, with reduction of the angiotensin II-binding capacity. None of the dietary electrolyte changes were accompanied by an ancrease in receptor affinity above the control value of 2 nM-1. A decrease in receptor affinity was noted after 6 wk of either low sodium or low potassium intake, when the renin and angiotensin II levels were increased by 104-129%. The adrenals of normal rats infused acutely with synthetic angiotensin II, or anesthetized with ether or sodium pentobarbital, which markedly increased plasma renin activity, contained fewer angiotensin receptors. These reductions in binding site concentration were not accompanied by changes in affinity and were attributed to occupancy by angiotensin II. These studies have demonstrated that chronic changes in sodium or potassium balance and acute changes in blood angiotensin II levels can exert modulating effects upon the adrenal content and/or affinity of specific receptor sites for angiotensin II.
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PMID:Regulation of angiotensin II receptors in the rat adrenal cortex by dietary electrolytes. 96 91

In the dog, the renin--angiotensin system appears to be a primary control mechanism for aldosterone secretion since angiotensin II blockade decreased aldosterone production to undetectable levels. Angiotensin II blockade also decreased cortisol secretion strikingly in dogs with thoracic caval constriction, a finding which suggests the presence of an angiotensin II receptor in the two inner zones of adrenal cortex. An important incidental finding after angiotensin II blockade in both sodium-depleted dogs and dogs with thoracic caval constriction was the striking drop in arterial pressure. It is suggested that angiotensin II acts on the peripheral arterioles to provide an important compensatory mechanism and, thereby, maintain arterial pressure in these low cardiac output states. In the rat, both the nonapeptide converting enzyme inhibitor and [Sar1, Ala8]-angiotensin II produced a marked decrease in aldosterone secretion in hypophysectomized, sodium-depleted animals. Both synthetic angiotensin II and its heptapeptide fragment produced striking increases in aldosterone secretion when the obscuring effect of ACTH was excluded in the rat. These findings provide evidence that the renin--angiotensin system is an important control mechanism for aldosterone biosynthesis in the rat.
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PMID:The use of angiotensin II blockade to study adrenal steroid secretion. 97 93

Acute renal failure was produced in rats by right nephrectomy and total occlusion of the left renal artery for 70 min. Angiotensin II competitive inhibitor, P113 (1-sar-8-ala-angiotensin II), was administered intravascularly for 100 min, starting 15 min before the clamping of the renal artery. A marked rise in plasma renin activity was observed 15 min after declamping and was significantly higher in the P113-treated rats than in saline-treated animals. The rise in plasma renin activity was observed 15 min after declamping and was similar in the two groups, indicating that P113 does not prevent the development of acute renal failure in this experimental model. It is suggested that the marked rise in plasma renin activity may be due to interruption of the normal feedback mechanisms which suppress renin release, as a result of occupation of the angiotensin II receptor sites by P113.
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PMID:High renin activity accompanying angiotensin II inhibition in rats with ischemic renal failure. 126

Regulation of the gene expression of type-1 angiotensin II receptor (AT1) by treatment with manidipine, a calcium channel blocker, or delapril, an angiotensin converting enzyme inhibitor, for one week was assessed in the adrenal gland, heart, kidney, and brain from spontaneously hypertensive rats (SHR). Tissue AT1 receptor messenger RNA (mRNA) content was measured by reverse transcriptase-polymerase chain reaction. Treatment with manidipine (3 mg/kg/day) or delapril (30 mg/kg/day) lowered systolic blood pressure (SBP) significantly (p < 0.01) (delta SBP; -73 mmHg or -67 mmHg, respectively). Although delapril markedly increased plasma renin activity (PRA), manidipine did not alter PRA. AT1 receptor mRNA content in the adrenal gland was significantly (p < 0.01) decreased by treatment with manidipine or delapril. In contrast, cardiac AT1 receptor mRNA content was significantly (p < 0.01) increased by treatment with either agent. There was no significant change in renal and brain AT1 receptor mRNA contents. These findings suggest that although the expression of AT1 receptor gene depends on the circulating renin-angiotensin system (RAS), it is regulated independently in a tissue-specific manner via the local RAS in each tissue of SHR.
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PMID:Regulation of the gene expression of type-1 angiotensin II receptor in spontaneously hypertensive rats. 134 80

The persistent effects on blood pressure of the angiotensin II receptor antagonist losartan and the converting enzyme inhibitor captopril were compared in the young spontaneously hypertensive rat (SHR). Losartan (DuP753/MK954, 15 mg/kg/day) and captopril (100 mg/kg/day) were given in the drinking water of 3-week-old SHRs for 4- and 10-week durations. Blood pressure was measured during treatment and after treatment was stopped until the age of 30 weeks. Both losartan and captopril given for 4 and 10 weeks prevented the development of hypertension during treatment and redevelopment of hypertension after treatment was stopped. Treatment for 10 weeks was more effective than for 4 weeks in lowering long-term pressure. Four weeks of treatment did not affect the mesenteric resistance artery media/lumen (m1/l1) ratio. In contrast, both losartan and captopril given for 10 weeks resulted in large and significant reductions in m1/l1 [5.3 +/- 0.8 and 5.63 +/- 0.8 vs 7.7 +/- 0.8 x 10(-2) (SD), p less than 0.001]. In losartan-treated rats, plasma renin and angiotensin II concentration were increased between 4- and 7-fold at the end of both treatment periods. These findings show losartan to be an effective antihypertensive agent and support data implicating angiotensin II in the early events leading to hypertension in this model. The abilities of losartan and captopril to affect blood pressure without affecting vascular structure suggest that the latter is a poor predictor of long-term hypertensive levels in the SHR.
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PMID:Angiotensin II receptor antagonist losartan has persistent effects on blood pressure in the young spontaneously hypertensive rat: lack of relation to vascular structure. 138 8

The regulation of the density of angiotensin II receptors in renal glomeruli in response to changes in salt intake is altered in Sprague-Dawley rats with renovascular hypertension due to aortic constriction, and in hypertensive salt-sensitive Dahl rats (Sahlgren 1989, Sahlgren & Aperia 1989). This study examines the modulatory role of sympathetic activity and arginine-vasopressin on angiotensin II receptors in hypertensive Sprague-Dawley rats with aortic constriction as well as in normotensive control rats. Denervation of the left kidney caused a 50% increase in the glomerular angiotensin II receptor density in the denervated kidney in both hypertensive rats and normotensive controls. An even more marked increase in glomerular receptor density occurred in both hypertensive rats and controls after blocking the sympathetic nervous system with guanethidine. To block the effects of arginine-vasopressin we used a blocker of the V1-receptors (predominant in vessels) and found an approximately 100% increase in the glomerular receptor density of angiotensin II in rats with aortic constriction. There was no reduction in blood pressure. Thus, on the receptor level the renin-angiotensin system is markedly influenced by the activity of other major pressor systems.
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PMID:Regulation of glomerular angiotensin II receptor densities in renovascular hypertension: response to reduced sympathetic and vasopressin influence. 149 64


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