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)

alpha-, beta 1- and beta 2-adrenergic receptors in the kidney mediate vasoconstriction, renin secretion and vasodilatation, respectively. Blockade of beta-receptors may therefore be expected to influence renal blood flow and possibly glomerular filtration rate by intrarenal effects as well as by reducing cardiac output and blood pressure. Since the various beta-adrenergic blocking drugs available differ in the degree to which they block beta 2-receptors (cardioselectivity) and also in their intrinsic sympathomimetic activity, they would be expected to have different effects on renal function. The acute administration of beta-blockers usually results in a reduction in effective renal plasma flow and glomerular filtration rate, whether or not the drug is cardioselective or has intrinsic sympathomimetic activity, with the exceptions of nadolol, which has actually increased effective renal plasma flow in some studies and of tolamolol. With chronic oral administration, the non-cardioselective beta-blockers reduced glomerular filtration rate and effective renal plasma flow. The cardioselective drugs do not usually produce significant reductions in glomerular filtration rate or effective renal plasma flow, although small increases in serum urea during treatment do occur. Interestingly, in contrast to findings with intravenous administration, orally administered nadolol produced a slight reduction in glomerular filtration rate in 1 study, so the effect of this agent on renal function under clinical conditions remains uncertain. It seems likely that beta-blockers reduce renal function predominantly by blocking beta 2-receptors in the kidney. To keep area of discussion in perspective, it is important to realise that although there have been isolated reports of serious deterioration in renal function coinciding with beta-blocker treatment, the great majority of reports are of reduction in glomerular filtration rate which are not of clinical significance, even in patients with pre-existing impairment of renal function. The beta-blockers with low lipid solubility-i.e. atenolol, nadolol and sotalol-are not metabolised, and their dose must be reduced in renal failure. Propranolol has active metabolites and its dose must also be reduced slightly in uraemia.
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PMID:Beta-blockers and renal function. 612 52

The acute and long-term haemodynamic effects of pindolol, practolol, alprenolol, oxprenolol, acebutolol, penbutolol, metoprolol, atenolol, propranolol and timolol in patients with uncomplicated hypertension as reported in the literature were analysed. The long-term effects of these beta-adrenoceptor antagonists on plasma renin activity and the concentration of noradrenaline in plasma were also reviewed. In spite of the many pharmacological and physicochemical differences the drugs appeared to have a hypotensive effect of approximately equal magnitude. The degree of cardiodepression and the suppression of plasma renin activity as exerted by the different beta-blockers were inversely correlated with their pharmacologically defined degree of intrinsic sympathomimetic activity (ISA). The increments in vascular resistance acutely after administration of a beta-blocker are proportional to the degree of cardiodepression, suggesting that increased vasoconstrictor nerve activity mediated through the baroreflex had prevented an acute fall in arterial pressure in response to a given fall in cardiac output. After long-term therapy the inverse correlation between changes in cardiac output and changes in vascular resistance is shifted to a lower level of vascular resistance. Plasma renin activity and vascular resistance are inversely correlated during long-term beta-blocker therapy for hypertension. Consequently, the fall in vascular resistance underlying the hypotensive effect of beta-blockers cannot be explained by suppression of plasma renin activity. Thus, cardiodepression and renin suppression are not essential for the hypotensive effect of beta-adrenoceptor antagonists. The accessibility of the central nervous system to the different beta-blockers neither determines the time of onset of blood pressure reduction nor the magnitude of this effect. If it is neither the blockade of postsynaptic beta-adrenoceptors in the heart or on juxtaglomerular cells, nor the blockade of central beta-receptors that can be held responsible for the blood pressure lowering efficacy of beta-adrenoceptor antagonists, one is left with the remaining possibility that blockade of presynaptic beta-receptors underlies the vasodilator and antihypertensive action of these drugs. Changes in the concentrations of noradrenaline in plasma are compatible with this supposition, provided that changes in clearance of noradrenaline from plasma are taken into account.
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PMID:Haemodynamic consequences of intrinsic sympathomimetic activity in relation to changes in plasma renin activity and noradrenaline during beta-blocker therapy for hypertension. 613

Ten subjects with hypertension received medroxalol, which blocks both alpha- and beta-adrenergic receptors, has intrinsic sympathomimetic beta 2-agonist properties and is a direct vasodilator. Renal function tests consisting of inulin clearance and p-amino hippuric acid (PAH) clearance, plasma renin activity (PRA) in recumbent and upright postures, and aldosterone excretion rate were performed. After intravenous medroxalol, inulin clearance and PAH clearance rose, renal vascular resistance fell, recumbent PRA was unchanged, and the rise in PRA with upright posture was blunted. After 1 mo on oral medroxalol, blood pressure was controlled while inulin clearance, PAH clearance, and renal vascular resistance were unchanged. The rise in PRA with upright posture remained blunted. Urinary aldosterone excretion was unchanged after 1 mo on medroxalol.
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PMID:Effects of medroxalol on renal function and the renin-angiotensin-aldosterone axis. 614 22

Bucindolol is a newly developed, nonselective beta-adrenergic blocking agent with intrinsic sympathomimetic activity and direct vasodilator properties. In 14 patients with mild to moderate essential hypertension, the effects of bucindolol, hydrochlorothiazide and their combination on blood pressure (BP), heart rate (HR) and parameters of the renin-aldosterone system were compared with those after placebo. Bucindolol's antihypertensive effect was evident within the first hour after drug administration, maximal at 2 to 3 hours, and lasted for as long as 12 hours. Compared with placebo values (108 +/- 5 mm Hg), both bucindolol (97 +/- 9 mm Hg) and hydrochlorothiazide (99 +/- 10 mm Hg) alone significantly and comparably reduced the 12-hour averaged standing diastolic BP, with the combination resulting in approximately additive effects (91 +/- 9 mm Hg). Although bucindolol alone did not affect HR, it attenuated the hydrochlorothiazide-induced increase in HR. There was a tendency for bucindolol to decrease plasma renin activity. Except for transient postural hypotension in 2 patients, bucindolol was well tolerated.
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PMID:Bucindolol, a beta-adrenoceptor blocker with vasodilatory action: its effect in systemic hypertension. 614 80

To investigate the possible effects of newly synthesized beta-adrenergic blockers on plasma renin activity, an assay was developed using unanesthetized mice and radioimmunoassay. Renin activity was significantly increased by the administration of hydralazine (1 mg/kg, i.p.), furosemide (20 mg/kg, i.v.), and isoproterenol (0.1 mg/kg, s.c.). Unlike isoproterenol, norepinephrine (1 mg/kg, s.c.) and epinephrine (1 mg/kg, s.c.) were active but considerably less effective stimulants. The increase caused by isoproterenol was blocked by clonidine, pindolol, bunolol, atenolol, and l-propranolol, but not d-propranolol. The beta-blockers with intrinsic sympathomimetic activity such as pindolol were found to increase renin activity when given alone, but blocked an increase in renin activity when given prior to isoproterenol. In general, nonselective beta-blocking drugs possessing both beta 1- and beta 2-(vascular) blocking activity were found to be most effective in blocking plasma renin activity on oral administration.
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PMID:Drug effects on plasma renin activity in the mouse. 617 84

Transection of subfornical organ efferents in the rat prevented the vasopressin release in response to intravenous angiotensin II infusion or following a small dose of the beta-sympathomimetic amine isoprenaline (30 micrograms/kg i.m.). In contrast, this lesion had no effect on vasopressin release after hypertonic saline injection or a high dose of isoprenaline (480 micrograms/kg i.m.). We conclude that blood-borne angiotensin II induces vasopressin release by acting on the subfornical organ; depending on the dose of isoprenaline, activation of the endogenous renin-angiotensin system may mediate isoprenaline-induced vasopressin release.
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PMID:Effect of transection of subfornical organ efferent projections on vasopressin release induced by angiotensin or isoprenaline in the rat. 628 92

Labetalol is a combined alpha- and beta-adrenoceptor blocking agent for oral and intravenous use in the treatment of hypertension. It is a nonselective antagonist at beta-adrenoceptors and a competitive antagonist of postsynaptic alpha 1-adrenoceptors. Labetalol is more potent at beta that at alpha 1 adrenoceptors in man; the ratio of beta-alpha antagonism is 3:1 after oral and 6.9:1 after intravenous administration. Labetalol is readily absorbed in man after oral administration, but the drug, which is lipid soluble, undergoes considerable hepatic first-pass metabolism and has an absolute bioavailability of approximately 25%. There are no active metabolites, and the elimination half-life of the drug is approximately 6 hours. Unlike conventional beta-adrenoceptor blocking drugs without intrinsic sympathomimetic activity, labetalol, when given acutely, produces a decrease in peripheral vascular resistance and blood pressure with little alteration in heart rate or cardiac output. However, like conventional beta-blockers, labetalol may influence the renin-angiotensin-aldosterone system and respiratory function. Clinical studies have shown that the antihypertensive efficacy of labetalol is superior to placebo and to diuretic therapy and is at least comparable to that of conventional beta-blockers, methyldopa, clonidine and various adrenergic neuronal blockers. Labetalol administered alone or with a diuretic is often effective when other antihypertensive regimens have failed. Studies have shown that labetalol is effective in the treatment of essential hypertension, renal hypertension, pheochromocytoma, pregnancy hypertension and hypertensive emergencies. In addition, preliminary studies indicate that labetalol may be of value in the management of ischemic heart disease. The most troublesome side effect of labetalol therapy is posture-related dizziness. Other reported side effects of the drug include gastrointestinal disturbances, tiredness, headache, scalp tingling, skin rashes, urinary retention and impotence. Side effects related to the beta-adrenoceptor blocking effect of labetalol, including asthma, heart failure and Raynaud's phenomenon, have been reported in rare instances.
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PMID:Labetalol: a review of its pharmacology, pharmacokinetics, clinical uses and adverse effects. 631 May 29

Potentiation of renin release can be achieved by combining adrenergic stimulation and renal vasodilatation. To examine whether pentobarbital anesthesia influences plasma renin concentration (PRC) by its vasodilatory effect, experiments were performed in rats subjected to increasing levels of adrenergic activity. PRC was two- to fourfold higher in anesthetized than in conscious rats when the beta-adrenoceptor agonist isoproterenol HCl (0.05-3.2 micrograms kg-1 min-1) was infused. The sympathomimetic agent tyramine suppressed and the alpha-adrenoceptor blocker phenoxybenzamine enhanced to the same extent the isoproterenol-stimulated PRC in conscious and anesthetized animals. Chronic renal denervation did not abolish the isoproterenol-pentobarbital synergistic effect on PRC. These results are consistent with the view that the renin response to pentobarbital anesthesia is somehow related to the vascular effects of the anesthetic.
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PMID:Potentiation of beta-adrenergic affects on plasma renin concentration by pentobarbital anesthesia. 631 31

Oxprenolol is a nonselective beta-adrenergic blocking agent that also possesses intrinsic sympathomimetic activity (ISA) and membrane stabilizing effects. Oxprenolol undergoes first pass metabolism with only 30% of an oral dose reaching the systemic circulation. The drug is approximately 80% protein bound and is eliminated primarily by glucuronidation in the liver. Less than 4% of oxprenolol is excreted unchanged in the urine. Oxprenolol may reduce the heart rate and prolong the effective and functional atrioventricular nodal refractory period. Oxprenolol has less negative inotropic and chronotropic effects than propranolol. Plasma renin activity is reduced; however, changes in plasma aldosterone level are not significant. Long term metabolic effects require further study. Oxprenolol appears to be comparable to other beta blockers in the treatment of hypertension and angina pectoris with no additional adverse reactions. If its partial agonist effect proves useful, it may have an advantage over other agents in treating patients with borderline cardiac reserve. Because of limited data, the use of oxprenolol for the treatment of arrhythmias, migraine, thyrotoxicosis, anxiety, and glaucoma cannot be recommended at this time.
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PMID:Oxprenolol hydrochloride: pharmacology, pharmacokinetics, adverse effects and clinical efficacy. 634 36

Eight out-patients with essential hypertension participated in a comparative, placebo-controlled study with a cross-over design. Pindolol and propranolol were administered orally in doses of 20.0 +/- 3.13 mg/d (mean +/- SEM) and 125.0 +/- 19.17 mg/d respectively. Pindolol reduced mean blood pressure by 11.9 mmHg; pre-ejection period index by 8.1 msec; total peripheral resistance by 3.1 mmHg min/L; and limb vascular resistance by 3.28 mmHg min 100 g/ml. Heart rate, cardiac output, plasma renin activity and urinary norepinephrine excretion rate were not altered by pindolol. Propranolol reduced mean blood pressure by 14.0 mmHg; heart rate by 9.1 beats/min; cardiac output by 0.57 L/min; limb blood flow by 1.06 ml/100 g.min; and plasma renin activity by 1.44 ng/ml/h; and increased pre-ejection period index by 8.7 msec. Total peripheral resistance, limb vascular resistance and urinary norepinephrine excretion rate were not altered by propranolol. It was concluded that: (1) the drugs, pindolol and propranolol, are equally effective as antihypertensive agents; (2) heart function and plasma renin activity are decreased by propranolol and unaltered by pindolol; (3) total peripheral resistance is decreased by pindolol and unaltered by propranolol; and (4) these findings may be explained by the intrinsic sympathomimetic activity exhibited by pindolol only.
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PMID:A comparative study on the effects of pindolol and propranolol on systemic and cardiac haemodynamics in hypertensive patients. 638 72


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