Comparative effects of bepridil and diltiazem on systemic blood pressure and isolated peripheral arteries in spontaneously hypertensive rats.

Bepridil and diltiazem were studied for their effects on blood pressure (BP) and heart rate (HR) of spontaneously hypertensive rats (SHR) and on vascular tone of femoral and mesenteric arterial strips from SHR. The drugs (i.v.) reduced BP and HR more markedly in SHR than in normotensive Wistar Kyoto rats (WKY). The effects of bepridil were less pronounced and less prolonged than those of diltiazem. Bepridil relaxed arterial strips precontracted by KCl or prostaglandin F2 alpha to almost the same extent as diltiazem in both SHR and WKY. Bepridil was almost as potent as diltiazem in inhibiting non-competitively the Ca2+-evoked contractions of arteries depolarized in a Ca2+-free, high K+ buffer. alpha-Adrenoceptor agonist-induced contractions accompanied and not accompanied by Ca2+ influx were inhibited more markedly by bepridil than diltiazem under certain conditions. The inhibitions were more marked in SHR than in WKY. Thus, it was suggested that both drugs acted as Ca2+ influx inhibitor to reduce vascular tone. Bepridil inhibited intracellular vasoconstriction mechanisms linked with alpha-adrenoceptors more potently than did diltiazem in SHR. Taken together, these actions can explain the antihypertensive properties of both drugs in SHR.