[Effects of nitrendipine on cardiovascular systems].
Cardiovascular effects of nitrendipine were examined in anesthetized dogs, blood-perfused canine papillary muscles and isolated arteries. In anesthetized dogs, nitrendipine by intravenous (0.3-10 micrograms/kg) or intraduodenal (0.1 mg/kg) administration lowered blood pressure and increased coronary and vertebral blood flow. Nitrendipine also decreased the difference in oxygen concentrations between arterial and coronary sinus blood, which indicates that nitrendipine increased the oxygen supply to the heart. Myocardial oxygen consumption was slightly increased at a low dose (3 micrograms/kg, i.v.) accompanied with a small increase in max dP/dt, but was decreased at high doses (30-100 micrograms/kg, i.v.). A negative inotropic effect was observed in blood-perfused canine papillary muscles. However, nitrendipine is thought to be highly vasoselective because much higher doses were required to decrease the myocardial contraction than to increase the coronary blood flow. Furthermore, nitrendipine suppressed the contraction induced by KCl, acetylcholine, histamine, norepinephrine, 5-hydroxytryptamine and prostaglandin F2 alpha of porcine coronary arteries, and the rhythmic contraction induced by 3,4-diaminopyridine of canine coronary arteries. In isolated rabbit aortic preparations, nitrendipine strongly inhibited the KCl-induced contraction, but not the phenylephrine-induced contraction. These effects of nitrendipine were almost similar to those of nifedipine. It is suggested that nitrendipine decreases afterload (blood pressure), increases the blood flow and oxygen supply to the heart, and inhibits coronary spasm, which is due to the calcium antagonistic effect. Nitrendipine may be useful for the treatment of ischemic heart diseases.
Kawahara
K
K
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Saitama, Japan.
Satoh
H
H
Inui
J
J
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009568:Nitrendipine / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D002121:Calcium Channel Blockers; D009568:Nitrendipine