Clinical and pharmacological properties of calcium antagonists in essential hypertension in humans and spontaneously hypertensive rats.
The abnormal cellular contractile mechanisms causing the development of essential hypertension in humans and rats were investigated, primarily with the use of Ca2+ and Ca antagonists. Helical strips isolated from mesenteric arteries of spontaneously hypertensive rats (Aoki SHR) showed an increased Ca2+ -induced tension development in the presence of noradrenaline or a high potassium concentration. The tension development of the SHR strips was greatly inhibited by Ca antagonists. In the patients with essential hypertension, both elevated blood pressure and elevated total peripheral resistance were reduced to normal levels by Ca antagonists. The drugs increased cardiac output and stroke volume. The hypotensive effect of the drugs was due to arterial vasodilation. We concluded that there might be an abnormally high sensitivity of the cell membrane system of vascular smooth muscle to both Ca2+ and Ca antagonists in patients with essential hypertension and in SHR. Abnormalities in Ca2+ channels, Ca2+ uptake, and Ca2+ binding of the cell membrane, which cause the high sensitivity, might greatly increase the Ca2+ levels of cytosol in the muscle. The increased cytosol Ca2+ induces, in turn, either increased contraction or decreased relaxation and a decrease in the arterial lumen. Any decrease in the lumen results in peripheral resistance enhancement, which is responsible for the increase in arterial blood pressure in essential hypertension. Thus, we propose the membrane theory of essential hypertension--that membrane abnormalities lead to hypertension.
D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D012083:Renin; D002118:Calcium; D009638:Norepinephrine