Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Rest and exercise hemodynamic and hormonal effects of nicorandil, a nicotinamide-nitrate vasodilator, were assessed in 9 patients with New York Heart Association class II or III congestive heart failure (CHF) and left ventricular ejection fraction less than or equal to 40%. Single oral doses of placebo and 40 and 60 mg of nicorandil were given in a double-blind, randomized trial. Hemodynamic measurements were assessed at rest, up to 8 hours after dose and at peak exercise performed on an upright cycloergometer 1 hour after the dose. Forearm blood flow and venous capacitance were measured by plethysmography 45 minutes after dose. Plasma noradrenaline and plasma renin activity were assessed 1 hour and 2 hours after dose, respectively. Data were analyzed by analysis of variance. Peak effects were observed between 30 and 60 minutes after dose. Mean blood pressure decreased from 86 +/- 7 mm Hg after placebo to 78 +/- 7 mm Hg after 40 mg (p less than 0.05) and to 78 +/- 7 mm Hg after 60 mg (p less than 0.05) of nicorandil. Mean pulmonary artery pressure decreased from 24 +/- 11 to 15 +/- 17 mm Hg (p less than 0.05) and to 17 +/- 7 mm Hg (p less than 0.05) and mean pulmonary wedge pressure decreased from 15 +/- 8 to 9 +/- 4 mm Hg (p less than 0.05) and to 10 +/- 5 mm Hg (p less than 0.05). The changes were significant up to 6 to 8 hours after both doses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Usefulness of nicorandil in congestive heart failure. 213 79

Plasma renin activity (PRA) was estimated in 30 patients with aluminium phosphide (AIP) poisoning (study group) admitted in shock. Ten patients in shock other than due to AIP poisoning (Group II A) and 20 normal healthy subjects (Group II B) served as controls. The PRA was significantly higher in the study group and group II A as compared to normal healthy subjects (p less than 0.001). Significantly higher PRA was found in the study group as compared to Group II A (p less than 0.001). The initial higher PRA continued to rise further in the study group but it started decreasing in Group II A as the duration of shock advanced. Continuation of shock in AIP poisoning was probably due to slow release of toxic PH3 gas, which was detected by positive silver nitrate paper test. The rise in PRA was directly proportional to the dose of pesticide consumed. There was direct relationship of mortality with increased PRA. Angiotensin converting enzyme inhibitors may have a role in combating shock in AIp poisoning.
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PMID:Plasma renin activity in shock due to aluminium phosphide poisoning. 220 Jul 84

Organic nitrates are well established in the treatment of a wide variety of cardiovascular disorders, most notably angina pectoris and congestive heart failure. However, attenuation of, or tolerance to, haemodynamic and anti-ischaemic effects may occur with all long-acting nitrate formulations. In the majority of patients continuous administration of long acting nitrates tends to promote the development of attenuation, while intermittent administration avoids it. Likewise, higher-doses appear to induce attenuation to a greater degree than lower doses. Attenuation of haemodynamic effects and exercise tolerance in heart failure patients, and of clinical end-points in angina patients, appears to be less than attenuation of exercise testing end-points in angina patients. While the use of intermittent therapy avoids the development of attenuation, it may expose the patient to an as yet undefined risk of silent and/or symptomatic anginal episodes occurring during the nitrate-free interval. Likewise, the role of concomitant therapy in avoiding this potential risk remains to be defined. Means of avoiding attenuation may include the coadministration of sulfhydryl donors such as N-acetylcysteine. Alternatively, angiotension-converting enzyme (ACE) inhibitors such as captopril may block renin-angiotensin system-induced reflex sympathetic stimulation. Attenuation may occur to a greater or lesser degree in individual patients. The proportion of attenuators vs non-attenuators remains to be defined, as does a means of identifying such patients prospectively by clinical and/or laboratory parameters. Conflicting results among smaller studies may reflect variable proportions of attenuators vs non-attenuators. However, conflicting results among larger studies may reflect differences in patient selection criteria, such as selecting patients with positive and reproducible stress tests and little in the way of spontaneously occurring angina versus selecting patients with positive but variable stress tests and frequent episodes of spontaneously induced angina. The former group may reflect pure fixed coronary artery disease with little in the way of vasospasm, or change in vasomotor tone, while the latter group may reflect greater variability in vasomotor tone and/or more in the way of plaque instability. The clinical efficacy of long acting nitrates might therefore be expected to be greatest in those patients with larger numbers of spontaneously occurring angina episodes. Recent data suggest that nitrates may have important direct effects on coronary vessels including dilating eccentric coronary stenoses, dilating intercoronary collateral channels and having greater dilating effects on more diseased segments as opposed to less diseased coronary segments.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Nitrate tolerance. A review of the evidence. 266 Nov 97

Isosorbide-5-mononitrate (IS-5-MN) is an active metabolite of isosorbide dinitrate with a longer plasma half life. Aim of the study was the evaluation of the effects of 40 mg/day of IS-5-MN on exercise capacity in patients with heart failure NYHA class II. After 1 week of wash-out, 10 patients with heart failure NYHA Class II, assumed 20 mg bid for 3 weeks. Bicycle ergometer tests were performed before (A), at the end of therapy (B), and 1 week later (C); in phase B the stress test was performed after 6 hours from the last assumption of IS-5-MN. We measured 24 hour urinary 6K-PGF1 alpha, the stable metabolite of prostacyclin, basal plasma renin activity (PRA) and plasma aldosterone, exercise-release of epinephrine and norepinephrine at the end of each phase of the study. The treatment with IS-5-MN improved the exercise capacity sigma (Watt.min), A less than (B = C), (p less than 0.01), while delta of heart rate (HR) during exercise (basal HR - maximal exercise HR)/(Watt.min), decreased, A greater than (B = C), (p less than 0.008). Basal BP and HR did not change. This fact seems consistent with the hypothesis of a combined effect of nitrates on both the venular and the arteriolar districts. Basal PRA and aldosterone, and catecholamine release during exercise after IS-5-MN did not change, while only norepinephrine increased 1 week after the end of the therapy, (A = B) less than C, (p less than 0.05): 24 hour urinary 6-K-PGF1 alpha increased after IS-5-MN A less than (B = C), (p less than 0.05). The results indicate that medium-term IS-5-MN treatment increases exercise capacity in patients with heart failure NYHA class II and that the effect lasts for 1 week after nitrate withdrawal at least. Prostacyclin is probably involved in medium-term clinical effect of IS-5-MN.
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PMID:[Effects of isosorbide-5-mononitrate on exercise capacity, prostacyclin synthesis, the renin-aldosterone axis and catecholamines in patients with cardiac insufficiency]. 275 47

To evaluate possible mechanisms underlying the development of nitrate tolerance, we treated 35 patients who had severe chronic heart failure with a prolonged (48-hour) intravenous infusion of nitroglycerin (6.4 micrograms per kilogram of body weight per minute) given either continuously or intermittently (12-hour infusions separated by intervals of 12 hours). Intravenous nitroglycerin produced immediate hemodynamic benefits in all patients, but the magnitude of this improvement was greatly diminished after 48 hours of continuous therapy with the drug. This attenuation was accompanied by cross-tolerance to oral isosorbide dinitrate and by an increase in heart rate, plasma renin activity, and body weight. In contrast, intermittent therapy with intravenous nitroglycerin was not associated with a loss of hemodynamic efficacy or cross-tolerance to oral nitrates and was not accompanied by changes in neurohormonal activity or body weight. In eight patients in whom nitrate tolerance developed during continuous intravenous therapy, the administration of the sulfhydryl-containing compound N-acetylcysteine (200 mg per kilogram orally) restored the hemodynamic state toward that observed at the start of the infusion of nitroglycerin (partial reversal of tolerance). In contrast, N-acetylcysteine had little hemodynamic effect in patients who were not receiving nitroglycerin. These data support the hypothesis that neurohormonal activation and depletion of sulfhydryl groups may interact to cause the loss of hemodynamic efficacy that occurs during prolonged treatment with intravenous nitroglycerin in patients with heart failure. Evaluation of the suggested role of sulfhydryl depletion in the development of tolerance will, however, require direct studies of vascular tissue.
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PMID:Prevention and reversal of nitrate tolerance in patients with congestive heart failure. 311 37

To investigate the relationship between tubular reabsorption of chloride and renal renin release in the isolated perfused rat kidney, perfusate renin activity was measured during substitution of either nitrate or thiocyanate for varying amounts of perfusate chloride but with maintained perfusate sodium concentration. Renin rose significantly as perfusate chloride fell; there was a sevenfold increase between perfusion with normal chloride and almost complete substitution of chloride by nitrate. With a normal perfusate chloride the addition of furosemide 10(-4) M to the perfusate also led to an increase in renin and a reduction in tubule chloride reabsorption. For all these experiments there was a significant negative correlation between renin and absolute tubular reabsorption of chloride (r = -0.68, P less than 0.001), but no such relationship with absolute sodium reabsorption. Renin release in a nonfiltering kidney, produced by elevating perfusate albumin concentration, increased approximately 40-fold. Thus increasing plasma oncotic pressure elevates renin by mechanisms additional to cessation of tubular chloride absorption. However, substitution of chloride in the perfusate by nitrate in this nonfiltering kidney did not further elevate renin release. We conclude that renin release is influenced by a signal dependent on, and inversely proportional to, chloride reabsorption in the thick ascending limb of the Loop of Henle.
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PMID:Effect of reduced chloride reabsorption on renin release in the isolated rat kidney. 390 51

AII occurs in the kidney at concentrations that greatly exceed those accounted for by trapped blood and is unaltered by prior perfusion of the kidneys to remove blood. Furthermore, kidney AII is unaltered by an infusion of AII at rates that double the plasma AII. The converting enzyme blocker SQ 20881 led to a fall in kidney AII and a rise in plasma renin activity (PRA). After dietary sodium deprivation, kidney AII, kidney renin, and PRA were all elevated. Sodium loading depressed plasma and kidney renin but did not alter intrarenal AII. In the two-kidney, one-clip renal hypertension model, kidney AII was elevated in the clipped kidney but unlike kidney renin was not suppressed in the contralateral kidney. Acute renal failure (ARF) induced by uranyl nitrate was associated with raised kidney AII and PRA, whereas no such changes occurred in glycerol-induced ARF. Replacement of volume losses in uranyl-nitrate-treated rats prevented the rise in PRA and the onset of ARF but not the rise in kidney AII. These findings are consistent with a local role of AII in the kidney.
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PMID:Angiotensin II: evidence for its role as an intrarenal hormone. 618 39

Prostaglandins (PG) stimulate renin secretion through a mechanism that does not require activation of the intrarenal vascular, macula densa (MD), or beta-adrenergic receptors. In the present study the isolated perfused rat kidney was used to study the role of PG as a mediator of renin secretion when extracellular calcium was decreased and after activation of each of the intrarenal receptors. A decrease in extracellular calcium resulted in an increase in renin (from 2.1 to 4.5 ng ANG I/ml, P less than 0.01) and a decrease in PGE2 excretion (from 102 to 44 pg X min-1 X g-1, P less than 0.01). PG synthesis inhibition with indomethacin did not attenuate the increase in renin secretion. Following beta-receptor stimulation with isoproterenol, there was an increase in renin (from 2.1 to 6.6 ng ANG I/ml, P less than 0.01) not associated with changes in PGE2 excretion and not prevented by PG inhibition. When the isolated vascular receptor was stimulated by perfusing either filtering or nonfiltering kidneys below the autoregulatory range of pressure, both renin and PGE2 production were increased, and the increases were prevented by PG inhibition. The MD was activated by three methods: eliminating distal nephron fluid delivery by perfusing with hyperoncotic albumin; perfusing at 60 mmHg in the presence of papaverine; and limiting chloride transport by partially replacing chloride with nitrate in the perfusate. In each circumstance renin and PGE2 production were increased and the increase was prevented by PG inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of prostaglandins in renin secretion in the isolated kidney. 633 Nov 73

The hemodynamic and hormonal responses to nitroglycerin administered transdermally in a gel-like matrix were evaluated in nine patients with severe congestive heart failure and in nine normal subjects. In normal subjects, peripheral vasodilation was accompanied by reflex sympathetic stimulation as reflected by an increase in heart rate and plasma norepinephrine. In patients with heart failure, nitroglycerin produced sustained hemodynamic effects that began 30 minutes after the application and fully persisted for at least 6 hours. A significant decrease in right and left ventricular filling pressures was associated with an increase in stroke index and a significant decrease in forearm and pulmonary vascular resistances. There was no change in heart rate and systemic arterial pressure or in plasma norepinephrine or plasma renin activity. After 24 hours, pressures had partially returned to control levels, but mean pulmonary artery pressure was still significantly lower than in the control period. After removal of the nitroglycerin, each patient exhibited a decrease in cardiac index and an increase, above the control values, in pulmonary and systemic arterial pressures and pulmonary, systemic and forearm vascular resistances. This transient rebound appeared to be unrelated to stimulation of the sympathetic or renin-angiotensin systems. Thus, transdermal absorption of this new form of nitroglycerin appears to provide a nitrate vascular effect that is sustained for 24 hours, but an endogenous vasoconstrictor effect may influence the hemodynamic response over the first 24 hours.
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PMID:Hemodynamic and hormonal response to transdermal nitroglycerin in normal subjects and in patients with congestive heart failure. 641 42

Continuous nitroglycerin (NTG) administration causes pharmacologic tolerance in humans and animals, whereas intermittent dosing is capable of avoiding or reducing tolerance development. The mechanism of NTG-induced hemodynamic tolerance may involve specific vascular desensitization and/or neurohormonal compensation. We compared effects of long-term (10 days) NTG administration (continuous or intermittent 12 h on/12 h off transdermal dosing, 10 micrograms/min) to rats with congestive heart failure (CHF) on radioligand binding from selected tissues. Tension responses in isolated blood vessels, plasma renin activity (PRA), plasma Na+ and K+ concentrations were also determined. The maximal binding values (Bmax) for [3H]glyburide and [3H]PN 200 110 in homogenates of left ventricle, right ventricle, and brain were not significantly different after NTG administration (continuous or intermittent), as compared with control. Intermittent, but not continuous, NTG caused significant increases in beta-adrenoceptor densities in the left ventricle, as judged by [3H]dihydroalprenolol binding (Bmax values: intermittent NTG 34.5 +/- 4.8, continuous NTG 24.4 +/- 2.6, placebo control 20.9 +/- 2.9 fmol/mg protein); Kd values for all ligands were not significantly altered by NTG administration. Both intermittent and continuous NTG increased the vascular contractile response to phenylephrine in isolated rat thoracic aorta. Slight reductions (two- to four-fold shifts in EC50 values) in thoracic aorta relaxant response to NTG were observed in both treatment groups as compared with control. Intermittent and continuous NTG administration caused selective changes in beta-adrenoceptor density and vascular response. These changes may contribute partly to the phenomenon of pharmacologic tolerance after chronic nitrate administration.
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PMID:Continuous versus intermittent nitroglycerin administration in experimental heart failure: vascular relaxation and radioligand binding to adrenoceptors and ion channels. 750 63


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