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)

The beta-adrenoceptor blocking properties and pharmacokinetics of bucindolol 150 mg were compared to those of propranolol 80 mg and a placebo in a double-blind trial in 6 healthy volunteers. Heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures and peak expiratory flow rate (PEFR) at rest and during vigorous exercise, and plasma renin activity (PRA) at rest, were measured before and at intervals up to 24 h after oral administration of the drugs. Bucindolol reduced exercise tachycardia and decreased exercise PEFR, thus behaving as a non-selective beta-adrenoceptor blocking drug. In contrast to propranolol, bucindolol did not reduce resting HR and PRA, probably because of its intrinsic sympathomimetic activity. It decreased resting DBP in relation to its peripheral vasodilator properties. The effects of bucindolol developed as early as 30 min after administration and lasted up to 24 h, whereas its Tmax and T 1/2 were 1.6 and 3.6 h respectively. Comparison of the time courses of plasma bucindolol and the cardiac beta-adrenoceptor blockade strongly suggests that in man bucindolol undergoes an extensive first-pass effect, leading to the formation of one or more active metabolites.
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PMID:Comparative beta-adrenoceptor blocking effect and pharmacokinetics of bucindolol and propranolol in man. 285 99

Abrupt withdrawal of beta-adrenoceptor antagonists may lead to "rebound-effects". To study the mechanism underlying this phenomenon, the effects of the nonselective beta-adrenoceptor antagonists propranolol [no intrinsic sympathomimetic activity (ISA)], alprenolol (weak ISA) and mepindolol (strong ISA) on lymphocyte beta 2-adrenoceptor density--assessed by (+/-)-[125I]-iodocyanopindolol (ICYP) binding--and plasma renin activity (PRA) were investigated in male healthy volunteers aged 23-35 years. Propranolol treatment (4 X 40 mg/day) increased the density of beta 2-adrenoceptors by 25% after 2 days; concomitantly PRA and heart rate were reduced. During treatment beta 2-adrenoceptor density remained elevated. After withdrawal of propranolol PRA reached pre-drug levels rapidly, while heart rate was significantly enhanced. Beta 2-Adrenoceptor density, however, declined slowly being still significantly increased after 3 days, although propranolol was not detectable in plasma after 24 h. The affinity of ICYP to beta 2-adrenoceptors was not changed during or after treatment. Mepindolol treatment (2 X 5 mg/day) caused a 30% decrease of beta 2-adrenoceptor density and PRA after 2 days; both parameters remained reduced during treatment. After withdrawal, PRA reached rapidly pre-drug levels, whereas beta 2-adrenoceptor density was still after 4 days significantly diminished. The KD-values for ICYP, however, were not changed. During and after treatment heart rate was not affected. Alprenolol treatment (4 X 100 mg/day) led to a rapid fall in PRA, but did not significantly affect beta 2-adrenoceptor density. It is concluded, that the ISA may play an important role in modulating beta 2-adrenoceptor density and hence tissue responsiveness to beta-adrenoceptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of beta-adrenoceptor antagonist administration on beta 2-adrenoceptor density in human lymphocytes. The role of the "intrinsic sympathomimetic activity". 285 31

Twelve beta adrenoceptor antagonists were examined for their effects on mean blood pressure (MBP), heart rate (HR), plasma renin activity (PRA) and sympathetic nerve function in spontaneously hypertensive rats (SHR). The selected drugs included cardioselective agents (acebutolol, atenolol and metoprolol), agents with intrinsic sympathomimetic activity (oxprenolol, acebutolol, alprenolol and pindolol) and agents with local anesthetic activity (propranolol, oxprenolol, acebutolol, alprenolol and labetalol). All 12 beta adrenoceptor antagonists, administered once daily for 4 days (30 mg/kg p.o.), significantly decreased MBP of SHR. This reduction in MBP was dissociable from both reductions in HR as well as peripheral beta adrenoceptor blockade. In addition, the onset of MBP reduction was slower than the onset of beta adrenoceptor blockade and became greater with duration of treatment. PRA activity was significantly and markedly reduced by both bunolol and metoprolol shortly after dosing at a time when HR was significantly reduced but MBP was not. Conversely, at a time when MBP was significantly reduced by both bunolol and metoprolol, PRA and HR were found to be normal. The changes in HR and PRA were correlated with peripheral beta adrenoceptor blockade but changes in MBP were not. Bunolol, metoprolol and propranolol had no consistent inhibitory effect on pressor responses to nerve stimulation in pithed SHR, although positive chronotropic responses to norepinephrine, tyramine, dimethylphenylpiperazinium and angiotensin I and II were significantly and markedly reduced. It is concluded that beta adrenoceptor antagonists, as a class, reduce MBP of conscious SHR, provided that sufficient time is allowed for this observation to occur. Furthermore, the reduction in MBP caused by beta adrenoceptor antagonists is unrelated to acute beta adrenoceptor blockade, changes in HR, reductions in PRA or inhibition of sympathetic nerve function. Finally, cardioselectivity, intrinsic sympathomimetric activity and local anesthetic activity are not required for the antihypertensive activity of these agents.
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PMID:Antihypertensive effects of 12 beta adrenoceptor antagonists in conscious spontaneously hypertensive rats: relationship to changes in plasma renin activity, heart rate and sympathetic nerve function. 287 38

The haemodynamic and renal effects of ephedrine were studied in 11 mechanically ventilated patients on the first day after major vascular surgery. Ephedrine, a sympathomimetic agent with alpha-1, beta-1, and beta-2 agonistic activity, was infused into 11 patients to achieve a 20% rise in systolic blood pressure. The doses used were 2-6 micrograms/kg/min, and in six of these 11 patients the dose was then doubled, 4-12 micrograms/kg/min for another renal function test. Blood pressure, heart rate, and cardiac output increased at both dose-ranges. Systolic pulmonary arterial pressure increased by 10% at the first dose-range. Systemic vascular resistance was unchanged and plasma catecholamine levels were unaltered in the present study. Plasma renin activity diminished by 18% and 6%, respectively. Clearance of para-aminohippuric acid increased by 20% and 6%, at the two dose-ranges, while clearance of inulin and urine flow rate increased by 24% and 29%, respectively, at the first dose-range, without further increase during the second dose-range. Fractional chloride excretion, and fractional osmolar clearance were unaltered. Fractional Na+ clearance rose by 30% and 36%, respectively. Fractional free water clearance diminished by 8% at the second dose-range. When comparing the two dose-ranges, HR, systolic and mean BP rose by 8%, 13% and 11%, respectively. Fractional K+ excretion diminished by 30%. We conclude that ephedrine given as a continuous infusion seems to have beneficial effects on renal function in patients after elective major vascular surgery.
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PMID:Effects of ephedrine on renal function in patients after major vascular surgery. 339 77

Vasodilator prostaglandins produced in the renal medulla have a role in blood pressure regulation, beyond modulation of sodium and water retention. Systemic vasodilation resulting from effects of renomedullary prostaglandins lowers systemic vascular resistance, and administration of NSAIDs elevates blood pressure in hypertensive patients treated with diuretics and/or beta blockers, in patients with myocardial infarction, and in patients taking sympathomimetic agents such as phenylpropanolamine. Aspirin, which appears in the urine as salicylic acid (which has no effect on cyclooxygenase) has not been implicated as a drug which attenuates blood pressure control. Similarly, sulindac, the active sulfide metabolite of which is not filtered, does not inhibit renal synthesis of prostaglandins, though given in doses sufficient to inhibit serum thromboxane and 6-keto PGF 1-alpha. In a double-blind complete crossover study of blood pressure and renal function in hypertensive patients controlled with timolol-hydrochlorothiazide, sulindac lowered blood pressure significantly, whereas naproxen and piroxicam significantly raised blood pressure, in the absence of any effect on GFR, plasma renin, weight, creatinine clearance, or urinary sodium. It is suggested that for arthritic patients with hypertension, the NSAIDs of choice are aspirin and sulindac.
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PMID:The arthritic patient with hypertension: selection of an NSAID. 354 Nov 67

The beta-adrenoceptor blocking effects and pharmacokinetics of bornaprolol (FM 24), a new beta-adrenoceptor blocking agent, have been compared with those of propranolol and a placebo in a double-blind trial in 6 healthy volunteers. Heart rate, systolic and diastolic blood pressures and peak expiratory flow rate were measured at rest and at the end of 3 min vigorous exercise on a bicycle ergometer, before and 2,24 and 48 h after single oral doses of bornaprolol (120, 240 and 480 mg) and propranolol (40, 80 and 160 mg). Plasma renin activity at rest and the plasma concentrations of the two drugs were determined. Bornaprolol significantly reduced resting heart rate, dose-dependently lowered exercise-induced tachycardia and decreased peak expiratory flow rate and plasma renin activity. In addition, exercise-induced tachycardia was significantly reduced by bornaprolol up to 48 hours after drug intake (pharmacodynamic half-life approximately 63-86 h) and there was a correlation between this reduction and the log plasma bornaprolol concentration over the 48-h period. Thus, bornaprolol behaved in man as a non-cardioselective and long-lasting beta-adrenoceptor blocking drug, probably devoid of intrinsic sympathomimetic activity.
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PMID:Beta-adrenoceptor blocking effects and plasma levels of bornaprolol and propranolol in man. 391 84

Continuous 6-h infusions of the beta adrenergic blockers d,l-propranolol or oxprenolol significantly reduced plasma renin activity (PRA) and mean blood pressure in the resting rabbit and prevented the stimulatory effects of isoproterenol on renin release and heart rate. These actions were due to blockade of beta receptors, for the inactive isomer, d-propranolol, had no effect. Despite sustained high plasma concentrations of d,l-propranolol (0.2 mug/ml) in the unstimulated animal, PRA did not fall below 36% of control values, suggesting that basal renin secretion is maintained partly by factors other than beta adrenergic mechanisms.Prindolol, another beta blocker, also abolished the effects of isoproterenol on renin and on the heart, and reduced blood pressure in the resting animal. However, prindolol increased resting PRA and heart rate, and in animals already receiving d,l-propranolol, it raised PRA and heart rate without further altering blood pressure. This suggests that the effect on PRA of prindolol was due to its intrinsic sympathomimetic activity and not hypotension-mediated mechanisms. The observation that the blood pressure-lowering effect of prindolol was associated with a rise in PRA, while another beta antagonist, H 35/25, lowered PRA but had no effect on blood pressure, indicates that the hypotensive action of beta blockers is unrelated to their effects on renin release. In both unstimulated and isoproterenol-challenged animals, only blockers possessing beta-1 receptor affinity (d,l-propranolol, oxprenolol, prindolol, practolol, and metoprolol) affected heart rate, while effects on PRA were more prominent with agents possessing beta-2 activity (d,l-propranolol, oxprenolol, prindolol, and H 35/25). Thus, the changes in PRA caused by the beta adrenergic blockers appear to be dependent upon the summation of their direct effects, antagonistic or sympathomimetic, on beta-2 adrenergic receptors regulating renin release.
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PMID:Comparison of the effects on renin release of beta adrenergic antagonists with differing properties. 415 50

The acute haemodynamic effects of the non-selective beta-adrenoceptor antiagonist pindolol which has considerable intrinsic sympathomimetic activity (ISA), were studied in 10 patients with essential hypertension for 24 h. One hour after oral dosing (10 mg), the drug reduced supine arterial pressure significantly. The maximum antihypertensive effect was observed after 3-4 h (-15 +/- 3%, P less than 0.001). The fall in arterial pressure was associated with a 25% reduction of systemic vascular resistance (P less than 0.001) after 24 h. By that time cardiac output was increased by 16 +/- 5% (P less than 0.05). Cardiac filling pressures and pulmonary artery pressure did not change. The vasodilator effect of pindolol cannot easily be explained by suppression of plasma renin activity since changes in arterial pressure and plasma renin were inversely correlated (r = -0.58, P less than 0.001). Despite the antihypertensive and vasodilator effect of pendolol, plasma noradrenaline did not rise. The rapid fall in arterial pressure and systemic vascular resistance may be explained by the absence of an initial reflex vasoconstriction which normally follows blockade of cardiac beta-receptors. This may be related to ISA on cardiac and vascular postsynaptic beta-receptors. Concomitant blockade of central and/or peripheral presynaptic beta-receptors is suggested by the absence of a rise in plasma noradrenaline and may contribute to the vasodilator action of pindolol.
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PMID:Direct 24-hour haemodynamic monitoring after starting beta-blocker therapy: studies with pindolol in hypertension. 610 Jul 55

1 The pharmacological effects and the pharmacokinetics of betaxolol (SL 75212), a new beta-adrenoceptor blocking agent, were compared with those of propranolol and a placebo in a double-blind trial involving six healthy volunteers. 2 Heart rate (HR), myocardial contractile force (MCF), systolic blood pressure (SBP) and peak expiratory flow rate (PEFR) were measured at rest and during vigorous exercise before and at intervals up to 25 h after oral administration of the drugs. In addition, plasma renin activity (PRA) at rest and blood levels of betaxolol and propranolol were determined. 3. Betaxolol proved to be a potent and long-lasting beta-adrenoceptor blocking drug, devoid of intrinsic beta-sympathomimetic activity. Its beta-adrenoceptor blocking action was shown to four-fold that of propranolol at the cardiac and renal levels and to last at least 25 h after drug intake. 4 The peak blood level of betaxolol was reached 2 to 4 hr after its administration, the first-pass loss is likely to be low and the half-life is 12.3 h. These pharmacokinetic data are perfectly consistent with the long duration of the pharmacological effects of betaxolol in man.
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PMID:Beta-adrenoceptor blocking effects and pharmacokinetics of betaxolol (SL 75212) in man. 610 73

The effects of long-term infusion of fenoterol (a beta 2-sympathomimetic drug) in combination with the calcium antagonist verapamil on water balance, the renin-angiotensin-aldosterone system and antidiuretic hormone during pregnancy were studied. Within two hours of the start of infusion, plasma renin and antidiuretic hormone levels were significantly increased, but plasma aldosterone was strongly decreased. There was a concomitant marked reduction of urinary, sodium, and potassium excretion and a decreased creatinine clearance. The long-lasting reduction of urinary excretion which resulted in an elevated water retention is apparently due to other unknown factors. Results are discussed with special regard to the relationship between water balance disturbances and pulmonary edema.
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PMID:The renin-angiotensin-aldosterone system, antidiuretic hormone levels and water balance under tocolytic therapy with Fenoterol and Verapamil. 610 79


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