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

The activity of renin in the blood plasma of 10-, 18--22-day and 2--3-month puppies is higher than in adult dogs. Blocking beta adrenoreceptors in 18--22-day, 2--3 month and adult animals decreases the activity of renin. Hypotensive effect following beta adrenergic block in 10-day puppies and alfa adrenergic block in puppies of all age groups is accompanied by the increase in renin activity. In early ontogenesis, the leading role in regulation of renin secretion belongs to changes in renal hemodynamics.
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PMID:[Effect of adrenoreceptor blockade on plasma renin activity during postnatal ontogenesis in dogs]. 3 8

Simultaneous patch-clamp and fura-2 measurements were used to investigate the electrical properties and receptor-mediated changes of intracellular calcium in renal juxtaglomerular cells. Here we report the presence of voltage-activated inward and outward rectifying potassium currents and the inhibition of the anomalous inward rectifying potassium current by angiotensin II (ANG-II). This action of ANG-II was mimicked by guanosine 5'-[gamma-thio]triphosphate but not by cAMP, cGMP, inositol 1,4,5-trisphosphate, or phorbol ester, suggesting that ANG-II inhibits the potassium channel directly by means of a guanine nucleotide-binding regulatory protein or by means of an unusual type of second messenger. Blocking of the inward rectifier was paralleled by membrane depolarization, but we obtained no evidence for calcium entry due to voltage-gated calcium channels in juxtaglomerular cells. Instead, under voltage clamp, ANG-II and guanosine 5'-[gamma-thio]triphosphate induced release of calcium from intracellular stores followed by a sustained phase of transmembrane calcium influx and oscillations of intracellular Ca2+ concentrations. Changes in intracellular Ca2+ concentrations were found to depend on the extracellular Ca concentration--i.e., the sustained elevation was abolished in absence of extracellular Ca, and the frequency of repetitive calcium release was directly related to the extracellular concentration of calcium. Moreover, an elevation of extracellular Ca concentration by itself induced release of intracellular calcium in the absence of other stimuli. Changes in intracellular Ca2+ concentrations were accompanied by prominent calcium-activated chloride currents, and this mechanism is inferred to be responsible for the inhibitory role of calcium in renin secretion. Intracellular application of cAMP but no cGMP inhibited ANG-II and guanosine 5'-[gamma-thio]triphosphate induced calcium mobilization in juxtaglomerular cells, being consistent with the facilitatory effects of elevated cAMP levels of renin release. The frequency of ANG-II induced oscillations was also markedly attenuated at depolarized membrane potentials suggesting effective negative feedback control of ANG-II-induced depolarization on repetitive Ca2+ transients induced by the hormone.
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PMID:Angiotensin II induces oscillations of intracellular calcium and blocks anomalous inward rectifying potassium current in mouse renal juxtaglomerular cells. 254 47

Renin plays a major role in the control of blood pressure and water and electrolyte metabolism and it is clear that blocking of this system is particularly effective in the treatment of essential hypertension and heart failure. A large number of converting enzyme inhibitors have been synthesized. Converting enzyme inhibitors are remarkably active in heart failure and they reduce microalbuminuria and possibly maintain glomerular function. Blocking of the renin-angiotensin system by converting enzyme inhibitors is not accompanied by hypotension or reflex stimulation of the sympathetic nervous system. Converting enzyme inhibitors represent a major therapeutic advance in the field of cardiovascular and renal disease but the long-term effects of decreased angiotensin II levels are unknown. There are other ways to inhibit the renin-angiotensin system. The recent discovery of orally-active non-peptide angiotensin II antagonists opens a range of fascinating prospects. Another approach consists in inhibiting the reaction of renin on angiotensinogen, which is remarkably selective. Although it is too early to know whether these new approaches will be less active, more active or as active as current converting enzyme inhibitors, they may constitute a progress in relation to currently available treatments.
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PMID:New therapeutic prospects of renin-angiotensin system inhibition. 269 Nov 25

The renal excretory function of rats was investigated under conditions of reduced extracellular fluid volume (ECV) obtained by peritoneal dialysis with isotonic glucose solution 10% of the body mass and using sodium-deficient diet (consisting of boiled rice) with intact renin-angiotensin system (RAS) and after angiotensin converting enzyme blockade by Captopril. The experiments were made on male Wistar rats placed in metabolic cages. The diuresis, the excretion of sodium, potassium, chlorine and osmotically active substances in spontaneously released urine were tested over a period of 6 hours. Captopril was administered with Alzet osmotic minipumps at 80 micrograms/h rate of infusion (in the experimental animals with peritoneal dialysis) and intraperitoneally 1 mg/kg (in the animals subjected to sodium-deficient diet). Blocking of the converting enzyme with Captopril was found to increase the diuresis, as well as the sodium and total osmotic excretion after peritoneal dialysis and under sodium-deficient regime. Blocking of RAS with Captopril reduced the adaptive possibilities of the organism in the cases of reduced ECV and sodium-deficient diet.
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PMID:Renin-angiotensin system and renal excretory function under conditions of hypovolemia and limited sodium intake. 353 91

beta-Blocking drugs suppress plasma renin activity (PRA) promptly. The current study was undertaken to document the return of PRA once blockade is withdrawn. In addition, we have correlated the return of PRA with both fall in plasma propranolol levels and change in blood pressure (BP). Fourteen patients established a baseline PRA. Propranolol hydrochloriode, 40 mg twice daily, was given for seven days and withdrawn abruptly. The PRA, plasma propranolol level, and BP were measured one and 12 hours after withdrawal, then every 24 hours. The PRA returns to baseline 12 hours after cessation of therapy. After withdrawal of therapy, there seems to be a "rebound" phenomenon in PRA, with elevations of 70% above baseline. This rebound also is demonstrated by a nonsignificant rise in BP. Plasma propranolol levels fall by; 70% within 13 hours of withdrawal. The decrease in propranolol levels closely correlates with the rise in PRA.
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PMID:Plasma renin activity suppression: duration after withdrawal from beta-adrenergic blockade. 610 71

The macula densa is a regulatory site for renin. It contains exclusively the neuronal isoform of nitric oxide synthase (NOS), suggesting NO could stimulate renin secretion through the macula densa pathway. To test whether neuronal NOS mediates renin secretion, renin was stimulated by either the renal baroreceptor or the diuretic furosemide (acting through the macula densa pathway). Renin secretion rate (RSR) was measured in 12 Inactin-anesthetized rats at normal (104 +/- 3 mmHg) and reduced renal perfusion pressure (65 +/- 1 mmHg), before and after selective blockade of the neuronal NOS with 7-nitroindazole (7-NI, 50 mg/kg ip). 7-NI had no effect on basal blood pressure (102 +/- 2 mmHg) or renal blood flow (RBF). Decreasing renal perfusion pressure doubled RSR from 11.8 +/- 3.3 to 22.9 +/- 5.7 ng ANG I.h-1.min-1 (P < 0.01) (ANG I is angiotensin I). Similarly, in 7-NI-treated rats, reduced perfusion doubled RSR from 8.5 +/- 1.8 to 20.5 +/- 6.2 ng ANG I.h-1.min-1 (P < 0.01). Renal hemodynamics and RSR were measured in response to 5 mg/kg iv furosemide in 12 control rats and 11 rats treated with 7-NI. Blocking neuronal NOS did not alter blood pressure (102 +/- 2 mmHg), RBF (5.8 +/- 0.4 ml.min-1.g kidney wt-1), or renal vascular resistance (18.7 +/- 1.4 mmHg.ml-1.min.g kidney wt).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Selective neuronal nitric oxide synthase inhibition blocks furosemide-stimulated renin secretion in vivo. 754 51

Intravenous injections of endotoxins from Escherichia coli or Salmonella minnesota stimulate drinking and reduce urinary excretion of water and solutes in rats. E. coli endotoxin (0.15 or 0.45 mg/kg i.v.) stimulated drinking without increasing plasma osmolality or sodium concentration, hematocrit, blood hemoglobin, or plasma protein concentration and without decreasing arterial pressure. Similarly, a dipsogenic dose of S. minnesota endotoxin (0.25 mg/kg i.v.) did not reduce arterial or venous pressures or change heart rate. Blocking the renin-angiotensin system with captopril or blocking histamine receptors with pyrilamine and cimetidine did not reduce drinking or urinary fluid retention caused by E. coli endotoxin. Injections of 10 or 450 ng E. coli endotoxin into a lateral cerebral ventricle increased body temperature but not water intake. In contrast to its stimulatory effect in water-replete rats, E. coli endotoxin (0.45 mg/kg i.v.) inhibited drinking in 24-h water-deprived rats. Thus we find no evidence to support the hypothesis that endotoxin causes thirst by changing known physiological signals of cellular or extracellular dehydration. The mechanism remains unknown.
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PMID:Endotoxin stimulates drinking in rats without changing dehydrational signals controlling thirst. 823 5

Through the multiple actions of angiotensin II (AII), the renin-angiotensin system (RAS) participates in cardiovascular homeostasis. Angiotensin II acts by binding to specific membrane-bound receptors, which are coupled to one of several signal transduction pathways. These AII receptors exhibit heterogeneity, represented by AT1 and AT2 receptor subtypes. The AT1 receptor mediates the major cardiovascular action of the RAS. This receptor has been cloned from multiple species, disclosing features consistent with a transmembrane, G-protein-linked receptor. Further AII receptor heterogeneity is evident by the cloning of isotypes of the AT1 receptor. Blocking the interaction of AII with its receptor is the most direct site to inhibit the actions of the RAS. Many AII receptor antagonists, including peptide analogs of AII and antibodies directed against AII, possess unfavorable properties that have limited their clinical utility. The discovery and further development of imidazole compounds with AII antagonist properties and favorable characteristics, however, has promise for clinical utility. The leader in this field is a selective AT1 receptor antagonist losartan (previously known as DuP 753 or MK-954). Losartan was demonstrated to be an effective antagonist of many AII-induced actions and an effective antihypertensive agent in many animal models of hypertension (HTN). Losartan also demonstrated secondary benefits in preventing stroke, treating congestive heart failure (CHF), and delaying the progression of renal disease in animal models. Clinical studies confirm the AII antagonist action of losartan and suggest that losartan will be effective in the treatment of essential HTN. AII antagonism is likely to provide useful treatment in essential HTN and CHF, conditions in which the RAS is known to play a major role. The utility of AII antagonism may extend beyond that of HTN and CHF, as suggested by the potential usefulness of angiotensin-converting enzyme (ACE) inhibition in the treatment or prevention of many other diseases. The key advantage AII antagonists provide over ACE inhibitors is that they may avoid unwanted side effects, related to bradykinin potentiation with the latter drugs. The AII antagonists will help determine the role of the RAS in physiologic regulation and in the pathophysiology of various disease states.
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PMID:Angiotensin II receptor blockade: an innovative approach to cardiovascular pharmacotherapy. 830 Aug 85

Craniotomy for resection of cerebral arterial venous malformation has been associated with postoperative hypertension, which necessitates administration of large doses of antihypertensive medications to control blood pressure. Controlling blood pressure is essential because hypertensive episodes can lead to postoperative cerebral hemorrhage with increases in morbidity and mortality. We measured vasoactive peptide and catecholamine release in 13 patients who underwent resection of an arterial venous malformation and in a control group of 6 patients who presented for clipping of unruptured cerebral aneurysms. Plasma renin activity, angiotensin I and II, vasopressin, aldosterone, epinephrine, and norepinephrine levels were measured intraoperatively and for 36 h postoperatively. Analysis of variance was used to assess sample and group effects. A significant interaction between sample and groups was found for norepinephrine (p < 0.001) and renin (p = 0.002). Our data suggest that elevated plasma renin and norepinephrine levels are in part responsible for postoperative hypertension in patients undergoing resection of arterial venous malformations. Blocking the release of these hormones may help control blood pressure after surgery for removal of arterial venous malformations.
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PMID:Analysis of catecholamine and vasoactive peptide release in intracranial arterial venous malformations. 882 55

In 10 anaesthetized cats, electroretinographic (ERG) measurements were carried out to further elucidate the involvement of bradykinin as a substrate component of the renin-angiotensin system in retinal neurotransmission. Reducing angiotensin II concentration by angiotensin-converting enzyme (ACE) inhibition increased sensitivity (0.5 log units) and gain (50%) of the rod b-wave amplitude. The b-wave implicit time was decreased only at high stimulus intensities (> 10(-2) cd/m). Blocking bradykinin receptors specifically decreased rod b-wave implicit time for all intensities, while its amplitude remained unaffected. Bradykinin effects were independent of alterations of angiotensin II activity. We therefore suggest that bradykinin influences inner retinal signal processing, hereby further supporting the hypothesis of a renin-angiotensin system involvement in retinal neurotransmission.
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PMID:Bradykinin receptor inhibition affects the rod b-wave in the cat electroretinogram. 899 85


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