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)

Calcium channel blockers have strong vasodilator, natriuretic and diuretic actions in normal and hypertensive subjects. The aim of this study was to evaluate the effect of diltiazem on renal function, renin-angiotensin-aldosterone axis (RAA) and atrial natriuretic factor (ANF) in patients with liver cirrhosis. Seven patients (3 females and 4 males) with a mean age of 56.3 +/- 11.1 years (36-68) entered the trial. All of the patients had HBV (6 cases) or HCV (1 case) related Child A (3 cases) or Child B (4 cases) liver cirrhosis proven by liver biopsy. Patients were given placebo for 15 days followed by p.o. diltiazem 30 mg t.i.d. for 15 days. Urinary volume, natriuresis, creatinine clearance, plasma renin activity (PRA), ANF and aldosterone (ALD) levels were determined after the washout period and during the first and second weeks of drug treatment. Urinary volume increased by 25-170% in 5 cases but this difference did not reach statistical significance. Slight increases in natriuresis occurred in some cases on the 3rd day of the trial but the overall results were not statistically significant (191.50 +/- 26.85 vs 204.07 +/- 39.83 mmol/l). Diltiazem induced no significant changes in PRA, ALD and ANF levels or creatinine clearance during the first or second weeks of the trial. There was a significant drop in the pulse rate on the first or second weeks of the treatment (p less than 0.01 and p less than 0.05, respectively). No significant changes were noted on mean arterial pressure (MAP).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of diltiazem on renal function in patients with liver cirrhosis. 183 38

The effects of diltiazem on hemodynamics, plasma catecholamine and plasma renin activity were studied during treadmill exercise test in 9 cases with moderate essential hypertension. Diltiazem of 120 mg/day was orally administered for 4 weeks. At maximum exercise, significant decrease in systolic blood pressure (-32 mmHg), heart rate (-16/min), pressure-rate product (-7,883 mmHg/min), plasma norepinephrine (-195 ng/L) and plasma epinephrine (-11 ng/L) were observed; while, diastolic blood pressure, ST depression and plasma renin activity showed no significant change. Also, a significant correlation between systolic blood pressure and plasma norepinephrine (r = 0.57, p < 0.001), especially after diltiazem therapy (r = 0.68, p < 0.001), was observed. These findings indicated that diltiazem can reduce the secretion of catecholamine from the sympathetic nerves during exercise in patients with essential hypertension.
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PMID:[Effects of diltiazem on hemodynamics, plasma catecholamine and renin activity during exercise in hypertension]. 184 25

Renin and catecholamine levels were determined in patients with mild to moderate hypertension before and after treatment with sustained release diltiazem or captopril and were correlated with the blood pressure response to these antihypertensives. Eight weeks of treatment with either agent led to equal decreases in both systolic and diastolic blood pressure. Pretreatment plasma renin activity (PRA) and plasma norepinephrine did not predict the blood pressure response to either agent. Diltiazem significantly increased both PRA and supine norepinephrine levels. However, in the diltiazem treated patients, there was no correlation between the change in plasma norepinephrine and the change in systolic or diastolic blood pressure. In contrast, there was a negative correlation (P less than .05) between the reactive rise in PRA and the decrease in systolic blood pressure. Thus, the antihypertensive response to a calcium channel blocker may be determined, in part, by the reactive response of pressor systems.
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PMID:Humoral factors determining the blood pressure response to converting enzyme inhibition and calcium channel blockade. 222 51

We undertook a systematic comparison of the effects of diltiazem and nifedipine and a nonspecific vasodilator, sodium nitroprusside, on renal perfusion, function, and activation of potentially relevant neurohormonal systems in the anesthetized dog. These agents were employed to reduce blood pressure to two levels, a mean arterial pressure level of 100-110 mm Hg, and a subtherapeutic level of 75-85 mm Hg. Renal plasma flow (ERPF) and glomerular filtration rate (GFR) were estimated as the clearances of p-aminohippurate and inulin, respectively. All studies with vasodilators were compared with a group which received placebo over an identical time period. The agents differed both in their action on the renal blood supply and in their activation of the renin-angiotensin-aldosterone and sympathetic nervous systems. ERPF was better maintained at both blood pressure levels with nitroprusside than with either diltiazem (p less than 0.005) or nifedipine (p less than 0.005). GFR was better maintained with nitroprusside and diltiazem than with nifedipine. The rise in plasma catecholamines and plasma renin activity was greatest with nifedipine, least with nitroprusside, and intermediate with diltiazem. Diltiazem was also associated with substantially less stimulation of aldosterone release than was nifedipine. Diltiazem and nifedipine are known to have greater renal vasodilator action when infused into the renal artery than nitroprusside. The better-sustained renal plasma flow and glomerular filtration rate during systemic administration with the latter may well reflect the role of calcium in renal autoregulation and the angiotensin-renin feedback loop. Despite an apparent shared mechanism of action, the calcium-entry-blocking agents differ sufficiently that therapeutic implications are possible.
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PMID:The renal response to diltiazem and nifedipine: comparison with nitroprusside. 241 90

The renal effects of the calcium entry-blocking drugs diltiazem, nifedipine, verapamil and nitrendipine are reviewed. Although nifedipine stimulates plasma renin activity on a short-term basis, none of the calcium entry blockers produces a clinically significant sustained effect on any of the components of the renin-angiotensin-aldosterone system. Although all of the calcium entry blockers effectively lower blood pressure, none adversely affects renal function; glomerular filtration rate and effective renal plasma flow are maintained. Diltiazem may increase glomerular filtration rate via attenuation of the intrarenal effects of angiotensin II or norepinephrine. Although diltiazem and nifedipine increase salt and water excretion on a short-term basis, none of the calcium entry blockers produces a clinically significant sustained effect on salt and water excretion; serum electrolytes, urinary sodium and potassium excretion, body fluid composition and body weight are unchanged. Thus, calcium entry blockers can be expected to assume a prominent role in the treatment of hypertension because of their ability to lower blood pressure while preserving renal perfusion and function.
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PMID:Effects of calcium entry blockers on renin-angiotensin-aldosterone system, renal function and hemodynamics, salt and water excretion and body fluid composition. 293 50

The sequence of intracellular events that lead to renin release is incompletely defined. Accordingly, we examined the interrelationship of two important factors in the process: renin release coupled to cAMP and renin release related to a decrease in intracellular calcium activity (Cai). Rat renal cortical slices were used to study these relationships in vitro. In the initial studies, cAMP-coupled renin release was established for isoproterenol (10(-5) M), prostacyclin (PGI2; 10(-6) M), and forskolin (10(-5) M). Each agent caused an increase in renin release and tissue cAMP levels, which were inhibited by the addition of the adenyl cyclase inhibitor 2',5'-dideoxyadenosine (DDA, 10(-5) M) to the media. Diltiazem (10(-4) M) and 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8; 0.6 X 10(-4) M) are believed to decrease Cai by different mechanisms; each of these agents caused a significant increase in renin release. Renin release stimulated by diltiazem, and TMB-8 was not inhibited by either DDA or indomethacin. The calcium ionophore A23187 (17 X 10(-6) M) and vanadate (10(-3) M) were next added to produce an increase in Cai. Both of these agents blunted renin release produced by isoproterenol, PGI2, and forskolin. These results provide strong indirect support for an inverse relationship between Cai and renin release in the juxtaglomerular cell. The results also imply that changes in Cai occupy a step that is distal to cAMP-coupled events in the sequence of intracellular events which culminate in renin release.
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PMID:Importance of calcium in renal renin release. 301 94

Twenty-seven patients with mild to moderate essential hypertension were randomized to receive therapy with either hydrochlorothiazide or diltiazem. After a placebo run-in period of 2 weeks, patients received increasing doses of either drug for 14 weeks. Those in whom hypertension was effectively controlled continued for 26 weeks of total treatment. Those not controlled, i.e. blood pressure greater than 140/90 mm Hg or less than 10 mm Hg reduction of pressure, were unblinded and crossed over to therapy with both drugs. Eleven of 14 patients (79%) were effectively treated with diltiazem alone, and 8 of 13 patients (62%) were effectively treated with hydrochlorothiazide alone. Supine blood pressures fell from 152 +/- 5/97 +/- 1 to 142 +/- 4/87 +/- 3 mm Hg in the 11 patients treated with diltiazem, from 152 +/- 2/99 +/- 1 to 134 +/- 3/88 +/- 2 mm Hg in the 8 patients treated with hydrochlorothiazide, and from 151 +/- 4/104 +/- 3 to 140 +/- 5/92 +/- 1 mm Hg in the 8 patients who received both drugs (p less than 0.01 for each group). Diltiazem patients had significant increases in alkaline phosphatase and urinary magnesium. Hydrochlorothiazide patients had increases in serum uric acid, serum globulin, CO2 content, and plasma renin activity. Serum potassium, serum chloride, urinary osmolality, and urinary calcium decreased after treatment with hydrochlorothiazide. Patients receiving both drugs had increases in serum glucose, serum BUN, serum uric acid, serum globulin, and CO2 content. These patients had decreased serum chloride and urinary calcium. Diltiazem monotherapy was comparable to hydrochlorothiazide in efficacy of lowering blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal-metabolic consequences of antihypertensive therapy with diltiazem versus hydrochlorothiazide. 332 Jul 20

The immediate effects of intravenous diltiazem effects and short-term (4 weeks) of the oral drug on systemic and regional hemodynamics, cardiac structure, and humoral responses were evaluated by previously reported methods in nine patients with mild-to-moderate essential hypertension and in one patient with primary aldosteronism. Diltiazem was first administered in three intravenous doses of 0.06, 0.06, and 0.12 mg/kg, respectively; patients were then treated for 4 weeks with daily doses ranging from 240 to 360 mg (average 300 mg). Intravenous diltiazem immediately reduced mean arterial pressure (from 115 +/- 3 to 96 +/- 3 mm Hg; p less than .01) through a fall in total peripheral resistance index (from 37 +/- 3 to 23 +/- 2 U/m2; p less than .01) that was associated with an increase in heart rate (from 66 +/- 2 to 77 +/- 3 beats/min; p less than .01) and cardiac index (from 3.3 +/- 0.3 to 4.3 +/- 0.4 liters/min/m2; p less than .01). These changes were not associated with changes in plasma levels of catecholamines or aldosterone or in plasma renin activity. After 4 weeks the significant decrease in mean arterial pressure persisted (104 +/- 3 mm Hg; p less than .01) and there were still no changes in the humoral substances or plasma volume. Renal blood flow index increased (from 368 +/- 52 to 462 +/- 57 ml/min/m2; p less than .01) and renal vascular resistance index decreased (from 0.37 +/- 0.06 to 0.26 +/- 0.04 U/m2; p less than .01), while splanchnic hemodynamics did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immediate and short-term hemodynamic effects of diltiazem in patients with hypertension. 351 85

The renal effects of the calcium entry-blocking drugs diltiazem, nifedipine, nitrendipine, nicardipine and verapamil are reviewed. Although nifedipine may acutely increase plasma renin activity, most of the calcium entry blockers have no sustained effect on any of the components of the renin-angiotensin-aldosterone system. Although all of the calcium entry blockers effectively lower blood pressure, none adversely affects renal function: Glomerular filtration rate and effective renal plasma flow are maintained. Diltiazem may increase glomerular filtration rate via attenuation of the intrarenal effects of angiotensin II or norepinephrine. Although all of the calcium entry blockers acutely increase salt and water excretion, most of the calcium entry blockers have no clinically sustained effect on salt and water excretion; serum electrolytes, urinary sodium and potassium excretion, body fluid composition and body weight are usually unchanged. Calcium entry blockers can be expected to assume a prominent role in the treatment of hypertension because of their ability to lower blood pressure while preserving renal perfusion and function.
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PMID:Short- and long-term effects of calcium entry blockers on the kidney. 354 86

The central and renal hemodynamic effects and the hormonal response to single doses of 60 mg and 90 mg of diltiazem were evaluated in 10 patients with severe chronic left ventricular (LV) systolic dysfunction (ejection fraction 0.22 +/- 0.08). Diltiazem administration resulted in only mild and mostly statistically insignificant changes. After 60 mg, only heart rate (from 86 +/- 10 beats/min at baseline to 79 +/- 14 beats/min at 4 hours) and pulmonary vascular resistance (from 231 +/- 108 to 165 +/- 74 dynes s cm-5 at 4 hours) changed significantly. Administration of 90 mg of diltiazem resulted in no significant change in any of the measured or calculated central hemodynamic variables. Individual data, however, revealed an increase stroke volume index in 3 patients but a decrease in 1 patient and a persistent increase in mean pulmonary artery wedge pressure in another patient. These hemodynamic changes were not associated with symptomatic deterioration in any of the patients. Both renal blood flow and glomerular filtration rate were impaired at baseline on both days and did not show a significant change 1, 2 and 4 hours after diltiazem administration. Similarly, no significant change was noted after either diltiazem dose in plasma catecholamine levels and renin concentration. In conclusion, administration of 60 to 90 mg of diltiazem in patients with severe chronic LV systolic dysfunction results in only mild and mostly insignificant acute effects on central and renal hemodynamics, plasma hormonal levels and patient clinical status.
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PMID:Central and renal hemodynamic effects and hormonal response to diltiazem in severe congestive heart failure. 355 52


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