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)

Plasma kallikrein releases bradykinin when activated by gram-negative septicemia or irreversible hemorrhagic shock. Pancreatitis releases glandular kallikrein causing hypotension and increased vascular permeability. Bradykinin in the brain produces hypertension. Renal kallikrein is released by high arterial pressure, vasodilators, low doses of noradrenaline, angiotensin II, mineralocorticoids and rapid volume expansion. It has a biphasic relation to sodium excretion. In essential hypertension, kallikrein release into the blood and urine is low and facilitates hypertension. High renin in Bartter's syndrome is balanced by high PGE and kallikrein without hypertension.
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PMID:Kallikrein, kininogen and kinins in control of blood pressure. 37 13

Plasma renin activity, blood angiotensin I, urinary kallikrein and blood bradykinin levels have been measured concurrently in rats over a range of daily sodium intake. Plasma renin activity, blood angiotensin I levels and urinary kallikrein were significantly increased by the low sodium diet (0.02 mmole per day). Bradykinin levels did not change. Plasma renin and blood angiotensin I were closely linearly related over the range of sodium intakes. Both were associated positively with urinary kallikrein excretion. Converting enzyme inhibition caused prompt, significant changes in plasma renin activity, endogenous circulating angiotensin I, and bradykinin. The changes in circulating hormone levels were dose dependent. Blood angiotensin I levels showed a greater responsiveness than blood bradykinin levels. Plasma renin activity and blood angiotensin I levels are closely related after converting enzyme inhibition. Both increased plasma renin, and impaired clearance of angiotensin I may contribute to blood angiotensin I levels. Difference in responsiveness of blood angiotensin I and blood bradykinin levels after inhibition suggests that other independent controls of the circulating levels of these hormones exist.
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PMID:Responses of the renin-angiotensin system and kallikrein-kinin system to sodium and converting enzyme inhibitor (SQ 14,225). 39 Sep 90

Endothelium-derived mediators are released in response to shear stress and a variety of endogenous substances including bradykinin and angiotensins. They may contribute to the regulation of the renin-angiotensin system in the vascular wall and in the kidney. Bradykinin is a powerful agonist at endothelial cells, and the actions of this peptide, which is generated by components of the vascular wall, during angiotensin-converting enzyme (ACE) inhibition may determine some of the vascular effects of ACE inhibitors. In vitro studies demonstrate that the relaxations to bradykinin are mostly endothelium dependent and are mediated by nitric oxide, endothelium-derived hyperpolarizing factor, and/or vasodilator prostaglandins; however, these endothelium-derived relaxing factors do not always contribute simultaneously to the relaxations in every artery. The contribution of ACE in the termination of bradykinin action, relative to the other inactivation processes (including carboxypeptidases and internalization) also may determine the ability of ACE inhibitors to augment the effects of the kinin. Furthermore, it appears that the level of ACE activity and the potency of bradykinin, respectively, are not uniform in all preparations. In arteries in which bradykinin is very efficacious and in which ACE activity may be relatively low, ACE inhibitors may prolong but not amplify the responses to the peptide. The pharmacologic characteristics of the responses of the different vascular beds to bradykinin, together with the modulation of endothelium-dependent responses to other agonists (including purines), may be of importance in the heterogeneity of the vasodilator actions of ACE inhibitors.
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PMID:Heterogeneity of endothelium-dependent vasodilator effects of angiotensin-converting enzyme inhibitors: role of bradykinin generation during ACE inhibition. 128 34

Angiotensin-converting enzyme (ACE) inhibitors exert their beneficial effects not only via endocrine mechanisms, but most probably also via interference with autocrine-paracrine actions involving local renin-angiotensin and kallikrein-kinin systems with subsequent autacoid release. Inhibition of ACE (kininase II) results in the reduction of angiotensin II generation and kinin degradation, leading to beneficial cardiovascular effects. Bradykinin and prostacyclin release from isolated rat hearts was increased by local ACE inhibitions with ramiprilat. In different models the bradykinin-mediated effects of ACE inhibition were abolished with the specific B2 kinin-receptor antagonist Hoe 140: The cardioprotective effects of ramiprilat or ramipril such as reduction of postischemic reperfusion injuries in isolated rat hearts or the reduction in infarct size in dogs and rabbits were abolished by coadministration of Hoe 140. Furthermore, left ventricular hypertrophy in rats with aortic banding could be prevented or regression was induced when the ACE inhibitor was given in a non-blood pressure-lowering dose. These beneficial effects were also abolished by Hoe 140. In conclusion, in different experimental models, ACE inhibitors exert cardioprotective effects. An enhancement of endothelial autacoid formation (nitric oxide and prostacyclin) by inhibiting degradation of bradykinin may contribute to these effects.
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PMID:Role of bradykinin in the cardiac effects of angiotensin-converting enzyme inhibitors. 128 35

1. Male, homozygous Brattleboro (i.e. vasopressin-deficient) rats were chronically instrumented with pulsed Doppler flow probes and intravascular catheters, and were studied 5 h after a subcutaneous injection of an hyperoncotic solution of polyethylene glycol to render them hypovolaemic, and hence dependent on the renin-angiotensin system for maintenance of haemodynamic status. Pilot experiments showed that, in this model, primed infusion of perindoprilat (0.05 mg kg-1 bolus, 0.05 mg kg-1 h-1 infusion) or captopril (0.2 mg kg-1 bolus, 0.2 mg kg-1 h-1 infusion) just abolished the pressor effect of angiotensin I (120 pmol), and had similar initial hypotensive and renal hyperaemic vasodilator effects. 2. Perindoprilat had more sustained hypotensive, and mesenteric and hindquarters vasodilator effects than captopril in the presence of saline. In the presence of NG-nitro-L-arginine methyl ester (L-NAME 3 mg kg-1 h-1), the renal vasodilator effects of perindoprilat were unchanged, whereas the other haemodynamic effects of perindoprilat and captopril were reduced. Hence, in the presence of L-NAME, all haemodynamic effects of perindoprilat were greater than those of captopril. 3. The renal hyperaemic vasodilator effects of acetylcholine were abolished by L-NAME and by perindoprilat, and were markedly reduced by captopril. However, since perindoprilat and captopril caused such marked renal hyperaemic vasodilatation themselves, it is feasible this change in baseline status contributed to their effects. It is unlikely this could be a full explanation of the results, because the haemodynamic effects of lemakalim were unchanged under any experimental conditions. 4. Bradykinin alone, or in the presence of saline, caused mesenteric hyperaemic vasodilatation whereas, in the presence of perindoprilat or captopril, bradykinin caused marked renal and mesenteric vasoconstrictions. However, in the additional presence of L-NAME, the mesenteric vasoconstriction was reduced, yet the hypotensive effect of bradykinin was augmented. One possible explanation of these observations is that, in the presence of L-NAME and either perindoprilat or captopril, bradykinin caused marked coronary vasoconstriction, leading to a reduction in cardiac output. 5. Neither perindoprilat nor captopril impaired the pressor, or renal, mesenteric, or hindquarters vasoconstrictor effects of L-NAME. Indeed, in their presence, the effects of L-NAME were generally enhanced, consistent with perindoprilat and captopril causing activation of nitric oxide-dependent mechanisms that were subsequently inhibited by L-NAME.
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PMID:Involvement of nitric oxide in the regional haemodynamic effects of perindoprilat and captopril in hypovolaemic Brattleboro rats. 146 39

Inhibitors of the angiotensin-converting enzyme (ACE = kininase II) by definition have a dual action: prevention of angiotensin II generation and inhibition of kinin degradation. Although the first mechanism is generally accepted, it may not by itself be sufficient to explain the acute blood pressure-lowering action of these compounds. Studies in experimental and clinical hypertension, including the use of selective angiotensin II and bradykinin receptor antagonists, suggest additional vasodilator, non-renin-dependent mechanisms in their action on blood flow and blood pressure. Inhibition of kinin degradation by ACE inhibitors will amplify kinin-mediated reactions on local vessel tone, in particular, if kinin generation is stimulated or this situation is experimentally mimicked by addition of exogenous bradykinin. The acute blood pressure-lowering action of ACE inhibitors is inhibited by indomethacin-type cyclooxygenase inhibitors, suggesting a contribution of bradykinin-induced release of vasodilator prostaglandins to their action. Bradykinin stimulates the phospholipase-dependent release of arachidonic acid from membrane phospholipids, allowing for subsequent generation of its metabolites, the eicosanoids. This stimulation is receptor-mediated and involves one or more types of B2 receptors, coupled via G-proteins to intracellular messenger systems that control cytosolic calcium levels. Bradykinin-induced changes in vessel tone are transient, caused by a rapidly developing tachyphylaxis at the receptor level. The potent vasodilator action of systemic bradykinin administration is not consistently reflected in studies performed on isolated blood vessels. This is probably due to the indirect nature of kinin-mediated vasomotor responses, i.e., the release of vasoactive mediators, most notably the eicosanoids and endothelium-derived relaxing factor (EDRF).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Converting enzyme inhibitors and the interaction between kinins and eicosanoids. 169 63

The present study on six anaesthetized dogs investigates the influences of two different vasodilators, bradykinin and papaverine, on the relationship between autoregulation of renal blood flow and glomerular filtration rate, sodium excretion and renin release. At control conditions renal blood flow and glomerular filtration rate was autoregulated to the same levels of renal arterial pressure, 55 +/- 3 and 58 +/- 3 mmHg, respectively. Renin release increased from 0.3 +/- 0.1 to 22 +/- 4 micrograms AI min-1, and sodium excretion decreased from 99 +/- 29 to 4.6 +/- 3.3 mumol min-1 when renal arterial pressure was reduced from 122 +/- 6 to 44 +/- 2 mmHg. Infusion of bradykinin (50 ng kg-1 min-1) increased renal blood flow by 50% at control blood pressure without changing glomerular filtration rate, and both renal blood flow and glomerular filtration rate autoregulated to the same pressure levels as during control. Sodium excretion increased threefold at control renal arterial pressure, but was unchanged at low renal arterial pressure. Bradykinin did not change renin release neither at control nor low renal arterial pressure. Papaverine infusion at a rate of 4 mg min-1 increased renal blood flow 50% without changing glomerular filtration rate. The lower pressure limits of renal blood flow and glomerular filtration rate autoregulation were increased to 94 +/- 6 and 93 +/- 6 mmHg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of bradykinin and papaverine on renal autoregulation and renin release in the anaesthetized dog. 181 77

Molecular, biochemical, and pharmacological data give evidence for a local renin angiotensin system (RAS). Infusion of angiotensin (ANG) I into the isolated perfused rat heart resulted in the appearance of ANG II in the venous effluent. In isolated working rat hearts with regional myocardial ischemia followed by reperfusion, angiotensin-converting enzyme (ACE) inhibitors were able to reduce the incidence and duration of ventricular fibrillation. Local ACE inhibition in the heart improved cardiodynamics, reduced enzyme release and increased the energy-rich phosphates in ischemic myocardial tissue. Bradykinin perfusion showed an identical fingerprint of effects, whereas ANG I or ANG II perfusion aggravated postischemic reperfusion arrhythmias and induced a deterioration of cardiodynamic and metabolic events. In different studies after myocardial infarction with congestive heart failure (animals and humans) it was demonstrated that long-term ACE inhibitor therapy prolonged survival. Furthermore, ACE inhibition increased exercise capacity in patients with myocardial infarction. In cardiac hypertrophy, ACE inhibitors capable of affecting tissue RAS can induce prevention and regression not only through their blood pressure lowering actions, but possibly also by direct cardiac effects, presumably by inhibition of local ANG II generation, a possible growth factor. These findings from experimental and clinical studies give evidence for cardioprotective effects of ACE inhibitors. Two to 3 days of pretreatment with 5 mg ramipril given as a once daily dose to hypertensive patients undergoing vascular surgery induced as increase in renin-like activity in carotid and renal arteries, as compared to normo- and hypertensives who did not receive ramipril medication before surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardioprotective effects of ACE inhibitors: experimental proof and clinical perspectives. 214 78

The hemodynamic and endocrine effects of bradykinin and kininogens were investigated using a closed-circuit isolated rat kidney perfused with angiotensin II (ANG II). ANG II induced vasoconstriction, stimulation of urinary kallikrein release, and inhibition of renin secretion. Bradykinin markedly increased renal perfusate flow (RPF) and produced a slight but significant diuresis and natriuresis. The inhibitory effect of ANG II on renin secretion was delayed. Urinary kallikrein secretion was unchanged. The effect of bradykinin was suppressed by the competitive kinin antagonist [DArg,Hyp3,Thi5,8,DPhe7]bradykinin. Kallikrein-sensitive rat high-molecular-weight kininogen produced a progressive rise in renal perfusate flow. Exocrine function and renin and kallikrein secretions were unchanged. Immunoreactive kinins, identified as bradykinin by high-pressure liquid chromatography, were liberated into the perfusate. Perfusate immunoreactive high-molecular-weight kininogen decreased in parallel as a result of consumption. The kalikrein-resistant T-kininogen was not hydrolyzed to release a kinin, had no effect on renal function, and its concentration in the perfusate remained constant. These results suggest that kinin can be produced in the renal circulation from kallikrein-sensitive circulating kininogens and can antagonize the vasoconstrictor effect of ANG II and alter renal hemodynamics. They provide evidence that the kallikrein-kinin system can participate with the renin-angiotensin system in the control of renal blood flow.
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PMID:Effect of bradykinin and kininogens in isolated rat kidney vasoconstricted by angiotensin II. 233 52

The effect of i. v. administration of angiotensin II, substance P, DSIP, B-endorphin and bradykinin on the behaviour and the somato-vegetative responses to electrical stimulation of negative and positive emotiogenic regions of the hypothalamus, were studied. Angiotensin II, substance P and DSIP suppressed the avoidance and self-stimulation responses and inhibited cardiovascular responses. Bradykinin, renin and B-endorphin increased the latency of avoidance responses, enhanced and prolonged the somato-vegetative responses to electrical stimulation of negative emotiogenic regions of the hypothalamus. Possible mechanisms of the peptides physiological activity are discussed.
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PMID:[Endogenous peptides in the organization of somato-vegetative responses to hypothalamic stimulation]. 241


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