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)

In normal man the sympathetic nervous system could exert an inhibitory influence on aldosterone responsiveness to angiotensin II. The possible role of alpha-1 adrenoceptors in the modulation of aldosterone response was assessed by studying the changes of plasma aldosterone during infusion of angiotensin II at the doses of 1, 2, 5 and 10 ng/kg.min or after corticotrophin injection, 0.25 mg, in 9 normal subjects before and after treatment with the selective alpha-1 adrenoceptor antagonist, prazosin. Prazosin, given during 3 weeks, did not modify supine arterial pressure, heart rate and the plasma levels of angiotensin II, renin, aldosterone or adrenaline but caused a significant (P less than 0.05) increase of plasma noradrenaline. The correlation relating plasma aldosterone to plasma angiotensin II levels before and during angiotensin II infusion and the response of plasma aldosterone to corticotrophin was not modified by prazosin. These findings suggest that in normal man there is no inhibitory influence of the noradrenergic system on aldosterone responsiveness to angiotensin II mediated by an alpha-1 dependent mechanism.
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PMID:Adrenergic activity and aldosterone regulation: no evidence for an alpha-1 adrenoceptor-mediated influence in normal subjects. 302 74

This study investigated whether the specific alpha-antagonist, prazosin, stimulated basal plasma renin levels and heart rate. Furthermore the beta-adrenergic nervous system was also investigated to ascertain whether it was involved in this effect. Prazosin (0.1 or 1 mg/kg) was injected subcutaneously (s.c.) to conscious normotensive rats, either alone or in combination with the beta-adrenoceptor antagonist, DL-propranolol (1 or 3 mg/kg). Rats bore chronically implanted dorsal aorta cannula for measurement of blood pressure and heart rate and blood sampling for renin determinations. Acute administration of prazosin (1 mg/kg, s.c.) produced a fall in mean arterial pressure accompanied by renin release and tachycardia. A tenfold lower dose of prazosin did not alter blood pressure or heart rate but did stimulate renin release. Acute administration of DL-propranolol, (1 or 3 mg/kg, s.c.) produced falls in blood pressure and heart rate but did not affect plasma renin level. Combinations of prazosin with propranolol gave falls in blood pressure similar to those predicted on the basis of a simple addition of the effects of the two drugs given separately. Prazosin-induced tachycardia and renin release were attenuated by propranolol. It appears that prazosin produces renin release and tachycardia via stimulation of the beta-adrenergic adrenoceptor.
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PMID:Effect of acute administration of prazosin on blood pressure, heart rate and plasma renin level in the conscious normotensive rat. 353 30

To determine the effects of the renin-angiotensin-aldosterone system on development of tolerance and fluid retention in patients with chronic congestive heart failure during long-term prazosin treatment, plasma renin concentration, aldosterone, norepinephrine and maximal exercise tolerance were measured during chronic therapy with digitalis and diuretics, to which prazosin, captopril or a combination of both drugs was added. Plasma renin concentration and aldosterone level decreased slightly during prazosin therapy and norepinephrine level increased significantly. When captopril was given, plasma renin concentration increased as expected, aldosterone level normalized and norepinephrine level decreased significantly. When prazosin was added to captopril therapy, norepinephrine level increased and plasma renin concentration and aldosterone level did not change. Exercise capacity did not increase during prazosin treatment, but was increased with captopril treatment. Prazosin treatment was associated with an increase in body weight even though the dose of furosemide was increased. Inhibition of the renin-angiotensin system did not prevent fluid retention induced by prazosin during combination therapy. These findings suggest that the renin-angiotensin-aldosterone system is not substantially involved in development of tolerance and fluid retention during prazosin therapy; stimulation of plasma norepinephrine may be of decisive importance.
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PMID:Contribution of the renin-angiotensin-aldosterone system to development of tolerance and fluid retention in chronic congestive heart failure during prazosin treatment. 354 7

Furosemide increases sodium (Na+) and potassium (K+) excretion but if dietary salt is provided, a compensatory reduction in Na+ and K+ excretion follows which restores neutral balances within 18 to 24 hours. This compensation is not interrupted by blockade of the renin-angiotensin-aldosterone system (RAA) alone with captopril. Since plasma norepinephrine concentration increases after furosemide and alpha 1 adrenoreceptors can mediate enhanced Na+ reabsorption, we administered prazosin (2 mg 6 hr-1) to six normal volunteers consuming a daily intake of 270 mmol of Na+ and 75 mmol of K+, and added captopril (25 mg 6 hr-1) for an additional day to block the RAA system concurrently. Furosemide (40 mg day-1) was given for the last four days. Prazosin given alone before the diuretic reduced (P less than 0.05) BP and plasma angiotensin II (AII) concentration and increased body weight and heart rate. However, when given with furosemide, neither prazosin nor prazosin with captopril modified the short-term natriuretic or kaliuretic responses to furosemide, or the ensuing compensatory reductions in Na+ and K+ excretion. Accordingly, cumulative balances for Na+ and K+ remained neutral over four days of diuretic administration. Neither drug altered the renal responsiveness to the diuretic which was assessed from the relationship between renal Na+ and K+ excretion and diuretic elimination. Although the BP was maintained when furosemide was given alone, when given with prazosin and captopril, the mean BP fell by 13 +/- 5 mm Hg (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Na+, K+, and BP homeostasis in man during furosemide: effects of prazosin and captopril. 355 Feb 14

Our subjects were seven severely hypertensive patients with blood pressures (BPs) over 140/90 who were using minoxidil, propranolol, and diuretics. Clonidine followed by prazosin was added to their regimen on an outpatient basis to establish the dose-response for BP and catecholamines. Plasma renin activity (PRA), body weight, and renal function were measured. Clonidine was given in doses of 0.2, 0.4, 0.6, and 0.8 mg/day. Supine and standing systolic BP decreased at all dose levels of clonidine (P less than 0.01, P less than 0.05). Diastolic BP decreased in the standing position with doses of 0.4, 0.6, and 0.8 mg (P less than 0.01, P less than 0.05). Subjects were hypernoradrenergic initially with plasma norepinephrine (PNE) 895 +/- 122 pg/ml. PNE was suppressed by 0.2 to 0.8 mg clonidine (P less than 0.01) with near maximal suppression at 0.4 mg daily. Systolic BP correlated with PNE (r = 0.59, P less than 0.001). Supine and standing PRA decreased after 0.2 mg clonidine (P less than 0.05) but not after higher doses. Our findings suggest the antihypertensive action of clonidine is related to PNE suppression but not to that of PRA. Plasma epinephrine (PE), body weight, and renal function did not change. Prazosin was given after clonidine to the same patients in a dose range of 3 to 40 mg/day. With doses of 6 to 40 mg, systolic and diastolic and supine and standing BP fell (P less than 0.001, P less than 0.01). PNE remained elevated throughout all dose levels and did not correlate with BP. Weight rose with prazosin (P less than 0.02) but PE, PRA, and renal function did not change. Hence, clonidine and prazosin induced additional lowering of BP but had different effects of PNE and weight.
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PMID:Clonidine and prazosin effects in hypernoradrenergic vasodilator-treated and beta-blocker-treated patients. 611 31

Prazosin was the result of an attempt to find a directly acting vasodilator drug with little or no effect on cardiac output, renin and salt and water metabolism. Clinical studies confirmed that these desirable features were possessed by prazosin in spite of an apparently peripheral mode of action and thus prazosin contrasted strongly with all other agents of this type. Prazosin differs from the classical alpha-adrenoceptor antagonists in possessing marked selectivity for alpha 1-adrenoceptors as opposed to alpha 2-adrenoceptors. This ensures the preservation of the local feedback control of the release of noradrenergic transmitter by the pre-junctional alpha 2-adrenoceptors. This fact appears to be responsible for the therapeutic success of prazosin and why prazosin is the first alpha-adrenoceptor blocking drug to be effective in the treatment of hypertension. The marked selectivity for alpha 1-adrenoceptors makes prazosin invaluable as a research tool, especially as a radioligand for the identification of alpha 1-adrenoceptors.
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PMID:The pharmacology of prazosin, an alpha 1-adrenoceptor antagonist and the basis for its use in the treatment of essential hypertension. 612 21

Prazosin, an orally active alpha-1 selective adrenergic antagonist, has been of value in treating patients with hypertension and congestive heart failure. In contrast to non-subtype-selective alpha-adrenergic antagonists and direct-acting vasodilators, prazosin's hypotensive action is accompanied by little or no increase in heart, rate, plasma renin, or plasma norepinephrine. Prazosin is a versatile drug that may be used alone or in combination to treat mild, moderate, or severe hypertension. The antihypertensive effect is sustained, and may increase during long-term therapy. The major side effect, postural hypotension after the first drug administration, is related to drug dose and intravascular volume depletion. Other side effects are mild and seldom limit therapy. In patients with congestive heart failure, prazosin results in balanced venous and arterial dilation, similar to that produced by nitroprusside. Attenuation of some or all of prazosin's initial hemodynamic effects has been seen during multiple short-term administrations. However, chronic studies have shown sustained symptomatic and hemodynamic improvement during long-term administration; initial hemodynamic attenuation may be transient or partial, and does not preclude long-term effectiveness, particularly during exercise. Preliminary studies indicate that prazosin may also be effective in treating patients with peripheral vasospasm due to Raynaud's phenomenon or ergotamine overdose.
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PMID:Alpha-adrenergic receptor blockade with prazosin. Consideration of hypertension, heart failure, and potential new applications. 612 97

Prazosin, a selective antagonist of postsynaptic alpha-adrenoreceptors, was used to investigate the influence mediated by the juxtaglomerular alpha-adrenoreceptors on renin release in man. We studied, in seven patients with essential hypertension, the acute effects of 0.25 mg prazosin, given intravenously, on blood pressure and plasma renin activity, the degree of alpha-blockade induced by the drug being assessed by comparing the increments in blood pressure following a test dose of phenylephrine before and after prazosin administration. We also measured the increments in plasma renin activity in response to beta-adrenergic stimulus consisting of an isoproterenol challenge, before and during the prazosin induced alpha blockade. Prazosin infusion caused, within 20 min, a marked reduction of the pressor response to phenylephrine, a significant increment in plasma renin activity, and no change in blood pressure. The increments in renin in response to isoproterenol were significantly greater, both in absolute and percent values, after rather than before prazosin. These results indicate that the increase in renin during systemic alpha 1-adrenoreceptor blockade may be independent of the fall in blood pressure and support the view that the juxtaglomerular alpha 1-adrenoreceptors participate in the regulation of renin release with an inhibitory action, which antagonizes the stimulating influence of the beta-adrenoreceptors.
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PMID:Dissociation of the effects of alpha 1-adrenergic blockade on blood pressure and renin release in patients with essential hypertension. 617 32

Eleven of 12 patients with severe congestive heart failure who were pretreated with diuretics and digitalis benefited from long-term therapy with prazosin which was titrated to the individual's maximally tolerated dose. Nine of the 11 patients improved their functional state by one (n = 4) or two (n = 5) New York Heart Association (NYHA) classes. Within 4 weeks the stroke volume index increased from 23 +/- 10 to 29 +/- 9 SD (ml/beat/m2) while pulmonary capillary pressure decreased from 29 +/- 8 +/- 9 mm Hg (p less than 0.05 for both) and peripheral vascular resistance fell from 2,245 +/- 792 to 1,603 +/- 355 dyn/s cm-5 (p less than 0.01). Hemodynamics results were similar on the same regimen in eight patients assessed for 6 months. Death of three patients (week 5 and week 17) was unrelated to prazosin therapy. Prazosin resulted in improved cardiac performance during leg-up-tilt or supine ergometry. Increase in stroke volume index was related to the fall in peripheral vascular resistance (r = -0.79, p less than 0.01). Plasma adrenaline (301 +/- 480 pg/Ml), noradrenaline (1,312 +/- 1,382 pg/ml), and renin activity (22 +/- 30 ng/ml/h) were in the range observed with pheochromocytoma; variables did not change on prazosin. This reflects an important role of alpha-adrenoceptor-mediated vascular regulation in patients with heart failure in whom long-term treatment with prazosin produces a sustained and well-tolerated vasodilator effect without further rise in catecholamines and renin.
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PMID:Clinical and hemodynamic improvement of congestive heart failure by long-term vasodilator therapy with postjunctional alpha 1-adrenoceptor blockade. 617 37

Patients with essential hypertension (n = 45) had significantly lower substance P plasma levels (13.6 +/- 2.30 pg/ml) in comparison with a group of 24 normotensive subjects (45.4 +/- 7.18 pg/ml) analyzed by radioimmunoassay. Prazosin treatment for 2 weeks with 4.5 mg/day enhanced the substance P plasma level depending on its antihypertensive effect. Norepinephrine concentration in plasma was also elevated by prazosin. Dipeptidylpeptidase IV, dopamine-beta-hydroxylase and plasma renin activity were not changed significantly. The results indicate the participation of substance P in pathophysiological processes of human essential hypertension.
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PMID:Evidence of decreased plasma substance P levels in human essential hypertension and influence of prazosin treatment. 619 65


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