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 paper reports the experiences of our group with 68 patients with progressive systemic sclerosis (PSS) admitted to hospitals of the University of Pittsburgh Health Center between 1955 and 1981 with scleroderma renal crisis (SRC). The onset of SRC was characterized by four features, namely, onset or aggravation, usually abrupt, of arterial hypertension; appearance of Grade III or IV retinopathy; elevations of peripheral renin activity to at least twice the upper limit of normal; and rapid deterioration of renal function within a period of less than one month. Over 90% of our patients in whom these criteria could be determined had at least three of them present with the onset of SRC. Management of these patients during the first 15 years of this period was uniformly ineffective. Before 1971, no patients lived longer than a year; usual survival ranged from 1 to 3 months. With the advent of renal dialysis and the more effective treatment of severe hypertension, along with the utilization of bilateral nephrectomy in selected anuric patients, some improvement in longevity was achieved. However, only in the past few years have we accumulated a group of 11 patients who have survived for longer than one year. The clinical characteristics of the onset and progression of SRC suggest the sudden imposition of severe stress such as cold or an autoimmune insult affecting vulnerable arteries and arterioles. The renal damage becomes self-perpetuating with extremely high renin activity causing further rise in blood pressure and additional renal and systemic vascular damage. Progress in the last few years seems to have been achieved primarily by the advent of pharmacologic agents that specifically block the effect of angiotensin II by inhibiting the angiotensin I converting enzyme. When diagnosis is prompt and the condition is treated as an emergency with these compounds, we and others have found that normal renal function can be restored in a number of patients. The result is a considerably brighter outlook for patients with this previously rapidly fatal complication of progressive systemic sclerosis.
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PMID:Hypertension and renal failure (scleroderma renal crisis) in progressive systemic sclerosis. Review of a 25-year experience with 68 cases. 635 55

Based on the retrospective analysis of 38 cases of renovascular hypertension treated by surgical intervention, the following indications are proposed for arterial reconstructive surgery: younger age of patient, short duration of hypertension, renin-mediated hypertension and extent and functional significance of the obstructing arterial lesion, favorable level of renal function in the affected side, and renal function threatened by advanced progressive vascular disease, surgically correctable lesion, and focal, unilateral renal arterial atherosclerosis without generalized atherosclerosis, good surgical risk, and hypertension not responding to medical treatment. Although the clinical use of the angiotensin I converting enzyme inhibitor and induction of percutaneous transluminal angioplasty can provide a new approach to non-surgical treatment for renovascular hypertension, the long-term use of antihypertensive drugs induces gradual decrease in renal function. Surgical treatment is best reserved for the patient on whom the available data meet the above criteria for vascular surgery.
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PMID:[Surgical treatment of renovascular hypertension with special reference to the indications for reconstructive surgery]. 637 7

The effect of inhibition of angiotensin I converting enzyme by captopril was studied in rats with aortic coarctation produced above the renal arteries. When captopril therapy was started before coarctation, blood pressure above the narrowing and the pressure difference across the coarctation were reduced, compared with values in animals with coarctation not given therapy. When captopril therapy was started 10 days after the coarctation, there was no effect on blood pressure. Plasma renin activity increased 24 hours after coarctation and returned to control levels by 5 days. Captopril caused an increase in renin activity and a decrease in plasma aldosterone concentrations. After 5 days, there was no difference in renin activity and plasma aldosterone levels between animals with coarctation given captopril therapy early and late and between appropriate controls. Our data suggest that the renin-angiotensin system is important in the early development but not in the maintenance of coarctation hypertension.
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PMID:Role of the renin-angiotensin system in hypertension after coarctation of the aorta. 638 92

The renin-angiotensin system is an exception among the various peptide hormone producing mechanisms in that it is an extracellular system. It was not clear whether renin in tissues other than kidney participates in the extracellular system or an intracellular mechanism. We examined the possibility of intracellular formation of angiotensin II in these tissues by using cloned, renin containing cells in culture as models. Neuroblastoma cells, pheochromocytoma cells, adrenal cortical cells and juxtaglomerular cells were shown to contain renin, angiotensin I and angiotensin II. Presence of angiotensin I converting enzyme was also demonstrated in some cell lines examined. Even juxtaglomerular cells in the intact kidney were shown to contain angiotensin I and angiotensin II by immunohistochemical technique. These findings indicate an intracellular mechanism of angiotensin II formation in various tissues and suggest that angiotensin II may have local paracrine functions.
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PMID:Local generation of angiotensin in the kidney and in tissue culture. 664 Sep 64

In order to evaluate the roles of the renin-angiotensin-aldosterone system and of catecholamines in 117 normotensive patients with chronic congestive heart failure (CHF), a study was made of the relationships between plasma concentrations, hepatic extraction of these humoral factors and hemodynamic parameters. In 6 patients with moderate to severe CHF, the acute effect of oral; administration of angiotensin I converting enzyme inhibitor, SQ 14225 (captopril), on mean arterial pressure (MAP), peripheral venous pressure (VP) and these humoral factors was investigated. In patients with CHF of Class III-IV (according to NYHA classification), the urinary norepinephrine (U-NE) excretion increased. Plasma norepinephrine (P-NE) levels increased in proportion to the severity of CHF (p less than 0.001) and had a positive correlation with systemic vascular resistance (SVR) (p less than 0.01), VP (p less than 0.05), pulmonary artery wedge pressure (PWP) (p less than 0.01) and plasma renin activity (PRA) (p less than 0.01). P-NE correlated negatively with the cardiac index (p less than 0.02). Hepatic extraction of norepinephrine (EX-NE) was reduced in patients with elevated right atrial pressure (RAP) (p less than 0.05) and negatively correlated with VP (p less than 0.05). In patients with elevated P-NE, U-NE increased significantly (p less than 0.01), despite their decreased renal clearance of norepinephrine (CNE) (p less than 0.02). There was no significant difference in EX-NE between these patients and patients with normal P-NE. PRA was higher in Class III-IV patients than in Class I-II patients in the prediuretic period (p less than 0.01). PA showed a significant positive correlation with PRA (p less than 0.001). Hepatic extraction of aldosterone (EX-A) was reduced in patients with elevated RAP (p less than 0.05) and was negatively correlated with VP (p less than 0.05). Following captopril administration, PRA increased consistently and PA decreased. MAP fell, especially in 2 patients with mitral stenosis. The heart rate tended to decrease. VP also fell with symptomatic improvement. The decline in VP was correlated with the decrease in P-NE (p less than 0.01). These findings suggest that the sympathetic nervous system contributes to the elevation of SVR and PWP even before frank heart failure develops. The rise of P-NE seems to be due to increased norepinephrine release from sympathetic nerve beds, whereas a decrease in hepatic extraction and renal clearance probably has only a minor effect. The renin-angiotensin system also seems to contribute to elevation of SVR, to maintain effective arterial pressure by enhanced sympathetic activity, and the renin-angiotensin system seems to be a main determinant of PA in CHF.
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PMID:A clinical study on the role of the renin-angiotensin-aldosterone system and catecholamines in chronic congestive heart failure. 675 73

The long-term effects of angiotensin I converting enzyme (kininase II) inhibition with Captopril on fluid and electrolyte metabolism, aldosterone secretion, renal function, and arterial pressure were evaluated in conscious sodium deficient dogs. Plasma aldosterone concentration (PAC), plasma renin activity (PRA), urinary sodium excretion (UNaV), arterial pressure (AP), renal blood flow (RBF), glomerular filtration rate (GFR), blood kinin concentration (BK), urinary kinin excretion (UK), and urinary kallikrein activity (UKA) were determined during long-term inhibition of angiotensin I converting enzyme (kininase II). In response to Captopril administration (20 mg/kg/day) PAC decreased from 38.9 +/- 6.7 to 14.3 +/- 2.3 ng/dl, PRA increased from 3.58 +/- 0.53 to 13.7 +/- 1.6 ng/ml/hr, UNaV increased from 0.65 +/- 0.27 to 6.4 +/- 1.2 mEq/day, AP decreased from 102 +/- 3 to 65 +/- 2 mmHg, RBF increased from 136 +/- 7 to 156 +/- 8 ml/min, GFR decreased from 65 +/- 8 to 36 +/- 7 ml/min, BK increased from 0.17 +/- 0.02 to 0.41 +/- 0.04 ng/ml, UK increased from 7.2 +/- 1.5 to 31.4 +/- 3.2 micrograms/day, and UKA decreased from 23.6 +/- 3.1 to 5.3 +/- 1.2 E.U./day. Aldosterone infusion in sodium deficient dogs maintained on Captopril failed to alter urinary sodium excretion, renal function, or arterial blood pressure. However, angiotensin II infusion (3 ng/kg/min) restored aldosterone secretion, renal function, and arterial blood pressure within three days to levels observed in untreated sodium deficient dogs. The marked alterations in renal function and urinary sodium excretion during angiotensin II infusion indicate that angiotensin II is several times more potent than aldosterone in the long-term control of sodium excretion. Also, our studies demonstrated that the long-term hypotensive and natriuretic actions of inhibitors of angiotensin I converting enzyme (kininase II) are mediated by inhibition of angiotensin II formation.
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PMID:Role of the renin-angiotensin-aldosterone and kallikrein-kinin systems in the control of fluid and electrolyte metabolism, renal function, and arterial blood pressure. 675 46

Various doses (5 mg, 12.5 mg and 25 mg) of angiotensin I converting enzyme inhibitor (SQ 14,255, captopril) were administered to 8 patients with essential hypertension on a three-crossover study design, and the time course of mean blood pressure (MBP), plasma renin activity (PRA), plasma angiotensin converting enzyme activity (ACE-A), plasma cortisol (PC) and plasma aldosterone (PA) were determined following administration of the drug. MBP fell in a dose dependent manner, and PRA showed a minor but significant increases in cases receiving 5 and 12.5 mg of the drug. A large and significant increase in PRA was observed following 25 mg of captopril. ACE-A was also reduced in a dose dependent manner. There was no difference between changes in PC at any of the three dose levels. The serum potassium concentration was determined before and 3 hr after 25 mg of captopril treatment and no significant change was observed. In spite of the dose dependent and theoretical changes in the above parameters, lowered responses of PA to each dose of the drug were shown in reverse order against an increasing dose. That is to say, the grade of fall in PA following 25 of captopril was smaller than that following the other doses of the drug, and 5 mg induced a greater decrease in PA than 12.5 mg. Based on these findings, the relatively high dose of captopril in the present study was apparently more effective in increasing some factors which suppressed reduction of PA by a fall in angiotensin II than a low dose of the drug.
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PMID:Effects of various doses of captopril on plasma aldosterone concentrations in patients with essential hypertension. 676 96

The effect of an oral angiotensin I converting enzyme inhibitor, SQ 14225 (Captopril) on blood pressure and plasma renin activity (PRA) was studied in deoxycorticosterone-salt (DOCA/salt) hypertensive rats. Intraperitoneal (ip) injection of captopril (1 mg/kg) produced a significant fall in systolic blood pressure (23.4 +/- 5.0 mm Hg, p < 0.001) whereas no significant change in blood pressure occurred in control rats. Indomethacin (IDM) (2.5 mg/kg ip) pretreatment significantly (p < 0.01) attenuated the hypotensive action of captopril in DOCA/salt rats. PRA was markedly suppressed in DOCA/salt rats (0.3 +/- 0.1 ng/ml/hr) when compared with the normotensive controls (4.4 +/- 2.2 ng/ml/hr, p < 0.001) at baseline. Captopril induced a significant rise in PRA in both groups of rats. These responses were not significantly altered by IDM pretreatment. The hypotensive effect of captopril in the DOCA/salt model may be mediated by prostaglandins since their synthesis is inhibited by indomethacin.
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PMID:Single-dose captopril administration in DOCA/salt rats: reduction of hypotensive effect by indomethacin. 700 6

The time courses of mean blood pressure (MBP), plasma renin activity (PRA), plasma aldosterone (PA), serum prostaglandin E (PGE), serum angiotensin I converting enzyme (ACE), and blood levels of angiotensin I converting enzyme inhibitor (SQ 14,225) (captopril) were studied in 6 patients with essential hypertension (5 men and 1 woman, aged 44 +/- 5.6 (mean +/- S.E.) years) before and 30, 60, 120 and 180 min after administration of 25 mg captopril. MBP and ACE began to fall within 30 min and reached a significant minimum between 60 and 180 min after captopril administration. PRA was significantly increased 60 min after captopril administration and continued for 180 min. On the other hand, PA had begun to fall significantly 180 min after captopril administration. The blood levels of captopril were significantly increased 30 min after captopril administration, with a peak at 120 min. The levels at 180 min were half the peak. The levels of PGE were not significantly changed within 180 min after captopril administration. These results suggest a discrepancy between the changes in MBP and the blood levels of captopril. The blood pressure lowering effect may be due to inhibition of angiotensin II (Ang. II) during the short-acting effect, and due to decrease of PA, metabolites of captopril, increase of kinin in the blood, inhibition of the slow pressor effect of Ang. II, increases of other depressor hormones such as prostacyclin and other depressor mechanisms during the long-acting effect.
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PMID:Relationship between blood pressure and blood levels of angiotensin I converting enzyme inhibitor (SQ 14,225). 702 28

Structural changes of the arteries in hypertension are determined by the unique genetics of the animals and by various growth promoters and growth inhibitors. Vascular smooth muscle cell growth promoting factors include fibroblast growth factor, platelet-derived growth factor, and vasoactive peptides such as norepinephrine, angiotensin II, and endothelin. Endothelial cells secrete three types of growth inhibiting factors. These are heparin--heparan sulfate, transforming growth factor beta, and nitric oxide. The effect of sympathetic innervation on vascular growth is probably dependent on its interaction with the renin-angiotensin system. In the mesenteric vascular bed, the elevated resistance in the arterial system is present in both the macroarteries and in the more distal microarteries and veins. Changes in resistance arteries include hypertrophy and reduction in outer diameter (remodelling). In the resistance arteries from human essential hypertensives, remodelling is the predominant finding. Long-term treatment with an angiotensin I converting enzyme inhibitor but not with a beta-blocker was effective in reversing this type of vascular change. Studies have suggested that in addition to angiotensin II, endothelin may play a role in vascular remodelling of resistance arteries.
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PMID:Pathophysiology of smooth muscle in hypertension. 758 23


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