Calcium entry blockers: antihypertensive and natriuretic effects in experimental animals.
Hypotensive and natriuretic effects of calcium entry blockers were studied in spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKYs). In SHRs, the hypotensive action of diltiazem was enhanced, while that of hydralazine was not different from its action in WKYs. Diltiazem, unlike hydralazine and nifedipine, did not cause reflex tachycardia in rats. Diltiazem and nifedipine caused an increase in urine volume and sodium excretion. The natriuretic potency of diltiazem was the same in both SHRs and WKYs and was not affected by pretreatment with indomethacin. Diltiazem increased plasma renin activity but had no influence on plasma aldosterone concentration. Hydralazine increased both plasma renin activity and plasma aldosterone concentration and decreased sodium excretion. In anesthetized dogs, diltiazem increased sodium excretion, glomerular filtration rate and renal blood flow. Diltiazem may have a direct effect on tubular sodium reabsorption. This assumption was supported by a study with short-circuit current of the isolated bullfrog bladder. It is likely that diltiazem's effect of increasing urine volume and sodium excretion is due mainly to changes in renal hemodynamics and partly to direct action on renal tubules. Diltiazem opposed angiotensin II-induced responses, such as renal vasoconstriction and reduction of glomerular filtration rate. Under this condition, a marked natriuretic effect was observed with both intravenous and intraarterial administration of diltiazem. The ability to increase urinary excretion of sodium is a desirable characteristic for an antihypertensive agent. Calcium entry blockers have this ability and are therefore able to act without causing sodium and water retention.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects; D009318:Natriuresis / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D011892:Rana catesbeiana; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects
D002121:Calcium Channel Blockers; D000804:Angiotensin II; D006830:Hydralazine; D004110:Diltiazem; D009543:Nifedipine