Factors involved in the antihypertensive action of calcium antagonists.
The main mechanism underlying the antihypertensive action of calcium antagonists is believed to be the vasodilation of peripheral vessels. To compare the effects of calcium antagonists with those of other vasodilators, nifedipine or its antihypertensive analog nitrendipine were tested in different normotensive and hypertensive rat strains and situations. The acute blood-pressure-lowering effect of nifedipine in the Dahl salt-sensitive rat was characterized by a rapid onset of action, the minimal effective oral dosage (0.1 mg/kg) being effective for up to 6 hours. Nifedipine was approximately 3 times more potent than hydralazine and equipotent to, but of shorter duration of action than, minoxidil. Natriuretic activity in normotensive Wistar and hypertensive Dahl salt-sensitive rats was observed with nitrendipine after an acute saline load (30 ml/kg by mouth), whereas vasodilators such as minoxidil and hydralazine decreased renal function under these conditions. Treatment of spontaneously hypertensive rats (SHR) with nifedipine in food (315 parts per million) for 60 weeks prevented the development of hypertension and resulted in decreased plasma renin activity and plasma aldosterone concentration in comparison to untreated SHR controls. Moreover, absolute and relative heart weights were reduced in the treated rats. Results suggest that the antihypertensive action of calcium antagonists, at least those of the dihydropyridine type, is not only due to peripheral vasodilation, since in contrast to other vasodilators a hyperdynamic circulation is not induced, the renin-angiotensin-aldosterone system is not activated, and sodium/volume retention cannot be expected because of a primary natriuretic effect. Therefore, a reduced volume load in addition to the decrease in afterload contributes to the antihypertensive effect of calcium antagonists and their prevention of heart hypertrophy.
D000450:Aldosterone / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005260:Female; D006830:Hydralazine / Q000494:pharmacology; D008297:Male; D008914:Minoxidil / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology*; D009568:Nitrendipine; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D011725:Pyridines; D014665:Vasodilator Agents; D006830:Hydralazine; D000450:Aldosterone; D008914:Minoxidil; D009568:Nitrendipine; D012083:Renin; D009543:Nifedipine