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 authors compared the effects of verapamil (120 mg three times daily for 3 days) with those of acute volume expansion with normal saline on the plasma levels of atrial natriuretic factors (ANF), renin (PRA), angiotensin II (AII), aldosterone (ALD), and arginine-vasopressin (AVP) in healthy subjects. A randomized, double-blind, placebo-controlled study of crossover design was employed, where each individual received two acute volume overloads 1 week apart, one during placebo and the other during treatment with verapamil. Verapamil reduced blood pressure (BP) and increased the plasma levels of ANF, PRA, AII, ALD, and AVP. Strong positive correlations were observed between PRA, AII, ALD, and AVP, but not with ANF. Acute volume expansion (1500 mL saline in 15 minutes, in supine legs-up position) similarly to verapamil increased ANF levels; however, opposite to verapamil, it reduced PRA-AII-ALD, did not modify AVP levels, and increased BP. The mechanisms of these changes are discussed. In verapamil-treated subjects, volume expansion produced an additional increase in ANF and inhibited the PRA-AII-ALD axis, suggesting that in young healthy individuals, verapamil does not interfere with the reflex compensatory hormonal mechanisms activated under circumstances of acute volume-salt overload, with rapid expansion of the central vascular compartment. Our study indicates that verapamil and volume expansion represent two different stimuli for ANF secretion associated with opposite changes in the PRA-AII-ALD axis. In addition, verapamil can be used as a tool to study and understand the simultaneous increases in ANF and in PRA, AII, and AVP, characteristics of congestive heart failure.
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PMID:Comparative effects of verapamil and volume overload on atrial natriuretic factors and the renin-angiotensin aldosterone-vasopressin system. 148 51

We have explored the effect of verapamil on renal hemodynamics and the renin-aldosterone system in ten patients with chronic renal disease and hypertension before and after 3 months of therapy. The mean +/- SEM glomerular filtration rates were 55 +/- 7 mL/min pre- and 55 +/- 8 mL/min posttherapy; the renal plasma flow was 231 +/- 29 mL/min pre and 244 +/- 35 mL/min posttherapy. The filtration fraction (0.24 pre; 0.23 post) and the renal vascular resistance (492 +/- 144 pre; 422 +/- 101 post) also remained stable with verapamil therapy. Blood pressure was lower after treatment (P less than .02) in 7 of 10 patients. Urinary albumin excretion was reduced only when blood pressure was lowered. Verapamil had a modest effect on the renin-aldosterone axis. While the mean increase in plasma renin activity from a pretreatment value of 1.8 +/- 0.42 ng/mL/h to 2.1 +/- 0.56 ng/mL/h failed to reach statistical significance, the increases in urinary aldosterone excretion from 8.2 +/- 2.2 mg/24 h to 11.1 +/- 2.3 mg/24 h did (P less than .001). Our results demonstrate that verapamil lowered blood pressure without renal hemodynamic compromise in hypertensive patients with chronic renal disease. The antihypertensive response was associated with a rise in urinary aldosterone excretion, with unchanged serum electrolytes. We conclude that verapamil is effective, safe, and well-tolerated in patients with renal impairment and hypertension, and may be suitable for clinical trials evaluating long-term progression of renal disease.
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PMID:Hemodynamic responses to verapamil monotherapy in patients with renal disease. 181 50

The effects of short- and long-term administration of the calcium-entry blocker verapamil on regulation of renal hemodynamics and renin release were analyzed in anesthetized dogs at controlled levels of renal perfusion pressure between 110 and 60 mmHg. The following three groups of dogs were studied: a control group, an acutely treated verapamil group (initial dose of 150 micrograms/kg followed by 4 micrograms.kg-1.min-1), and a chronically treated verapamil group (240 mg per os twice each day). At 110 mmHg the renal blood flow (RBF) in the acutely and chronically treated groups was 53% greater than (P less than 0.03) and 79% greater than (P less than 0.01) that of the control group. Glomerular filtration rate (GFR) in the acutely and chronically treated groups was 64 and 92%, respectively, greater than (P less than 0.01 for both) that of the control group. Autoregulation of RBF and GFR was extremely effective in the control group, whereas it was severely impaired by acute and long-term treatment with verapamil. Renin release at 110 mmHg in the control and the acutely treated groups were similar, 3.36 +/- 0.96 and 4.46 +/- 0.64 U.min-1.g-1, respectively, although in the chronically treated group the rate of release was 8.89 +/- 2.60 U.min-1.g-1 (P less than 0.03). As perfusion pressure was reduced, the rate of release from the acutely treated group rose to higher levels than that of the control group; at 70 mmHg release from the acutely treated group was 88% greater than that of the control group (P less than 0.01). Verapamil profoundly alters regulation of renal hemodynamics and renin release and the effect is prominent during both short- and long-term administration.
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PMID:Regulation of renin release and renal hemodynamics during acute and chronic verapamil administration. 218 71

The acute renal failure associated with cyclosporine may result from vasoconstriction of intrarenal arterioles. To evaluate the mechanism of cyclosporine-induced nephrotoxicity, we acutely administered cyclosporine to eight healthy female volunteers with normal blood pressure and renal function. Cyclosporine (4 mg/kg) in 250 ml of 5% dextrose in water (D5W) was administered as a steady intravenous infusion over 6 hr. Glomerular filtration rate and renal plasma flow were measured by serum disappearance of 99m TcDTPA and 131I hippuran, respectively, during the last 3 hr of the infusion. D5W was given to the patients on separate days before the cyclosporine infusion to obtain control data. Systolic and diastolic blood pressure measured every hour during the infusions and renal vascular resistance were slightly higher during cyclosporine administration, but the increases were not statistically significant. Renal plasma flow was not affected by cyclosporine, being 479.6 +/- 24.9 ml/min during the control infusion and 463.3 +/- 12.7 ml/min during the cyclosporine infusion. However, glomerular filtration rate was reduced by cyclosporine in all patients (control, 108.8 +/- 2.5 ml/min, vs. cyclosporine, 91.1 +/- 2.2 ml/min, P less than .01), except one who demonstrated no significant change. Urinary excretion of thromboxane B2 during cyclosporine administration was markedly increased in all patients, being 39.9 +/- 8.2 ng/hr in the control period and 85.8 +/- 22.3 ng/hr during cyclosporine infusion (P less than .05), except for the one patient in whom no decrease in GFR was noted. There was no significant change in the urinary excretion rate for 6-keto-prostaglandin F1a or prostaglandin E during cyclosporine infusion. Serum averaged levels of peripheral renin activity, angiotensin II, and aldosterone did not change during with the cyclosporine administration compared with the control. All patients demonstrated a decrease in 24-h urinary excretion of sodium and potassium on the day of the cyclosporine infusion. Verapamil SR (240 mg daily for 7 days prior to cyclosporine infusion) did not reverse the reduction in glomerular filtration rate induced by cyclosporine; however, a significant reduction in renal vascular resistance and an increase in renal plasma flow (P less than .05) were noted when the volunteers were treated with both verapamil and cyclosporine compared with cyclosporine alone. Intravenous infusion of Cremophor EL, the vehicle to dissolve cyclosporine, demonstrated no significant effects on blood pressure, renal hemodynamics or urinary prostaglandin excretion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acute effects of intravenous cyclosporine on blood pressure, renal hemodynamics, and urine prostaglandin production of healthy humans. 230 Oct 25

The effect of administration of amphotericin B (AMPHO) on renal hemodynamics was studied in the rat. Acute infusion (1.2 mg/kg) of AMPHO resulted in a significant fall in glomerular filtration rate (GFR) (0.82 vs. 1.33 ml/min, P less than .01) and renal plasma flow (3.38 vs. 6.24 ml/min; P less than .01) and a rise in renal vascular resistance (23.55 vs. 11.25 mm Hg.min/ml; P less than .05) compared with base-line values. Administration of AMPHO (5 mg/kg/day i.p.) for 21 days resulted in similar changes in GFR, renal plasma flow and renal vascular resistance. Pretreatment of rats with the angiotensin II receptor blocker, sar-gly angiotensin II, did not prevent the renal vasoconstriction or fall in GFR with AMPHO. Unilateral renal denervation did not prevent the decreased GFR or effective renal plasma flow after AMPHO when compared with the contralateral, innervated kidney. Pretreatment of rats with verapamil completely inhibited renal vasoconstriction during and after AMPHO. Verapamil markedly attenuated the fall in GFR observed during AMPHO (AMPHO + verapamil vs. AMPHO + vehicle; 0.73 vs. 0.26 ml/min; P less than .05); however, the GFR observed in the postinfusion period was significantly decreased (base line vs. final; 1.17 vs. 0.84 ml/min; P less than .01). The authors conclude that 1) the adverse renal hemodynamic effects of AMPHO are not directly mediated by the renin-angiotensin or renal sympathetic nervous systems and 2) pretreatment with verapamil completely prevents AMPHO-induced renal vasoconstriction.
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PMID:Adverse effect of amphotericin B administration on renal hemodynamics in the rat. Neurohumoral mechanisms and influence of calcium channel blockade. 245 76

In 14 patients with arterial hypertension secondary to chronic renal parenchymal disease and impaired renal function, 24-h ambulatory blood pressure, casual blood pressure, plasma concentrations of angiotensin II, aldosterone, arginine vasopressin and atrial natriuretic peptide, serum creatinine, plasma lipids and lipoproteins, and body weight were determined at the end of two consecutive 3-week periods; placebo was administered in the first period and verapamil sustained-release 240 mg was given in the second period. Verapamil reduced mean 24-h ambulatory blood pressure from 152/104 mm Hg (means) to 142/97 mm Hg. Blood pressure was reduced significantly during the daytime, in the evening, and in the early morning, but not at night. Casual blood pressure was also significantly reduced from 176/106 mm Hg to 154/96 mm Hg. No significant changes were determined in the hormones, serum creatinine, plasma lipids and lipoproteins, heart rate, or body weight. Atrial natriuretic peptide was correlated significantly with serum creatinine (p = 0.733, n = 14, p less than 0.01). We conclude that verapamil sustained-release 240 mg in one daily dose has a moderate blood-pressure-lowering effect in patients with chronic renal disease and hypertension without inducing tachycardia, activation of the renin-angiotensin-aldosterone system, or increase in body weight, and without altering renal function and plasma lipids and lipoproteins. The positive correlation between atrial natriuretic peptide and serum creatinine may support the hypothesis that extracellular volume increases during progression of renal disease.
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PMID:Verapamil sustained-release in renal parenchymal hypertension: effect on blood pressure, kidney function, angiotensin II, aldosterone, arginine vasopressin, atrial natriuretic peptide, and lipoproteins. 247 77

Seven healthy male volunteers were studied at the end of 7 days placebo period and after 7 days treatment with verapamil (120 mg twice daily). Verapamil increased significantly plasma renin activity and urinary excretion of 6-keto prostaglandin F1 alpha without significant modification of plasma aldosterone. Metoclopramide (10 mg i. v.) induced a significant increase of plasma aldosterone with the peak values 15 min after the injection of the drug. The results indicate that verapamil does not lead to secondary hyperaldosteronism which is characteristic of most other vasodilators. The increase of prostacyclin, measured as 6-keto prostaglandin F1 alpha can contribute to the efficacy of verapamil in patients with ischemic heart disease and hypertension. The present study suggests that the aldosterone response to metoclopramide is not directly dependent on calcium, but an indirect effect of calcium through renin-angiotensin system cannot be excluded.
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PMID:Effect of verapamil on renin-angiotensin-aldosterone system, urinary 6-keto prostaglandin F1 alpha and aldosterone response to metoclopramide in normal man. 263 2

Although verapamil is a well-established treatment for angina, cardiac arrhythmias and cardiomyopathies, this review reflects current interest in calcium antagonists as anti-hypertensive agents by focusing on the role of verapamil in hypertension. Verapamil is a phenylalkylamine derivative which antagonises calcium influx through the slow channels of vascular smooth muscle and cardiac cell membranes. By reducing intracellular free calcium concentrations, verapamil causes coronary and peripheral vasodilation and depresses myocardial contractility and electrical activity in the atrioventricular and sinoatrial nodes. Verapamil is well suited for the management of essential hypertension since it produces generalised systemic vasodilation resulting in a marked reduction in systemic vascular resistance and, consequently, blood pressure. Evidence from clinical studies supports the role of oral verapamil as an effective and well-tolerated first-line treatment for the management of patients with mild to moderate essential hypertension. Clinical studies have shown that verapamil is more effective the higher the pretreatment blood pressure and some authors have found a more pronounced antihypertensive effect in older patients or in patients with low plasma renin activity. Sustained release verapamil formulations are available for oral administration which, as a single daily dose, are as effective in lowering blood pressure over 24 hours as equivalent doses of conventional verapamil formulations given 3 times daily. As a first-line antihypertensive agent, oral verapamil is equivalent to several other calcium antagonists, beta-blockers, diuretics, angiotensin-converting enzyme (ACE) inhibitors and other vasodilators, and is not associated with many of the common adverse effects of these treatments. Verapamil may be preferred as an alternative first-line antihypertensive treatment to diuretics in elderly patients because it has similar efficacy in these patients without causing the adverse effects commonly linked with diuretic treatment. Furthermore, because verapamil does not cause bronchoconstriction, it may be used in preference to beta-blockers in patients with asthma or chronic obstructive airway disease. Reflex tachycardia, orthostatic hypotension or development of tolerance is not evident following verapamil administration. As a second- or third-line treatment for patients refractory to established antihypertensive regimens, verapamil produces marked blood pressure reductions when combined with diuretics and/or ACE inhibitors, beta-blockers and vasodilators such as prazosin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Verapamil. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension. 267 May 11

In 14 patients with arterial hypertension secondary to chronic renal parenchymal disease and impaired renal function, 24-h ambulatory and casual blood pressure readings plasma, angiotensin II, aldosterone, arginine vasopressin and atrial natriuretic peptide, creatinine clearance, plasma lipids and lipoproteins, and body weight were determined after consecutive 3-week periods on placebo and sustained release verapamil 240 mg/day. Verapamil reduced the mean 24-h ambulatory blood pressure from 152/104 to 142/97 mm Hg. Blood pressure was significantly reduced during the daytime and the evening, but not at night. Casual blood pressure was also significantly reduced from 176/106 mm Hg to 154/96 mm Hg. No significant changes were found in the hormones, creatinine clearance, plasma lipids and lipoproteins, heart rate or body weight. The atrial natriuretic peptide level was significantly correlated with the calculated creatinine clearance (r = -0.797). Thus, sustained release verapamil 240 mg as a single daily dose had a moderate hypotensive effect in patients with chronic renal disease without inducing tachycardia, activation of the renin-angiotensin-aldosterone system, or increasing body weight, and without altering renal function and plasma lipids and lipoproteins. The negative correlation between atrial natriuretic peptide and glomerular filtration rate supports the hypothesis that the extracellular volume increases during progression of renal disease.
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PMID:Sustained release verapamil in renal hypertension. 296 36

Experiments were conducted in two-kidney, one-clip renal vascular hypertensive rats (GHR) to assess the responses of each kidney to acute treatment with the antihypertensive calcium channel blocking agent verapamil in the presence and in the absence of converting enzyme inhibitor (CEI). One group of GHR (0.2 mm inner diam. clip 3 weeks before study) were examined during a control period, and during a second period of infusion of verapamil (600 micrograms h-1 kg-1). A second group of GHR were examined during a control period, during CEI (teprotide, 3 mg h-1 kg-1) infusion and during a third period of verapamil (600 micrograms h-1 kg-1) infusion superimposed on CEI infusion. Although systemic blood pressure (BP) decreased from 175 +/- 4 to 149 +/- 5 mmHg (mean +/- SEM) in response to verapamil alone, renal blood flow for non-clipped kidneys increased from 5.9 +/- 0.4 to 6.5 +/- 0.3 ml/min, indicating a 30% reduction of renal vascular resistance (P values less than or equal to 0.01; n = 9). Glomerular filtration rate (GFR) for non-clipped kidneys (n = 24) increased from 0.91 +/- 0.09 to 1.47 +/- 0.14 ml/min and filtration fraction increased from 0.32 +/- 0.04 to 0.47 +/- 0.03 (P values less than or equal to 0.05). Urine flow rate and absolute and fractional sodium excretion for non-clipped kidneys increased. GFR for clipped kidneys decreased during verapamil. Treatment with CEI alone resulted in nearly identical responses of BP and function of the non-clipped kidney, except filtration fraction was unchanged. The addition of verapamil to ongoing converting enzyme blockade tended to augment the increased GFR of the non-clipped kidney. Plasma renin activity (PRA) increased from 30 +/- 3 to 59 +/- 7 ng of angiotensin (ANG) I h-1 ml-1 with verapamil alone, a significantly larger increment than the increase of PRA from 27 +/- 5 to 39 +/- 9 ng of ANG I h-1 ml-1 in GHR subjected to comparable blood pressure reduction by mechanical aortic constriction. Verapamil resulted in many similar effects on renal function to those observed during blockade of converting enzyme. The increased filtration fraction observed in response to verapamil may be the result of vasodilatation of the afferent arteriole or of an increase in the glomerular ultrafiltration coefficient.
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PMID:Effects of verapamil and converting enzyme inhibition on bilateral renal function of two-kidney, one-clip hypertensive rats. 303 14


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