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Cardiovascular effects of brovincamine and possible mechanisms involved
Abstract:
Cardiovascular effects of brovincamine (BV) and possible modes of action were studied in dogs, rabbits and guinea-pigs. In pentobarbitone-anaesthetized dogs, intravenous administration of BV (1.6-12.8 mg/kg) induced a dose-dependent decrease of blood pressure and heart rate, a slight and transient stimulation of respiration, and a prolongation of the R-R interval in ECG without changes of wave pattern. In the isolated atria of guinea-pigs, BV showed no effect at 10(-7) and 10(-6) g/ml, but dose-dependently inhibited both myocardial contractile force and heart rate at the higher concentrations of 10(-5) and 10(-4) g/ml. In pentobarbitone-anaesthetized dogs, BV (0.1-1.6 mg/kg) administered to the vertebral or carotid artery dose-dependently increased the blood flow in the respective artery. Intravenous administration of BV (0.8-12.8 mg/kg) also exhibited a dose-dependent increase of the vertebral and carotid blood flow, but the increase was a little reduced at the higher dose of 12.8 mg/kg, probably resulting from marked hypotension and negative chronotropism. Intravenous administration of BV at 6.4 mg/kg induced a marked increase of the coronary flow, a slight increase of the renal flow and a slight decrease of the femoral flow. 11-Bromovincaminic acid (BVA, 0.1, 0.2 mg/kg), a major metabolite of BV, given intravenously or to the internal carotid artery, did not exert actions on the blood pressure, heart rate and carotid blood flow, implying that it is an inactive metabolite. In rabbit pulmonary arterial strips, BV showed no influence on effects of noradrenaline and adenosine but inhibited KCl-induced contracture. This inhibitory effect of BV, but not papaverine, was antagonized by an increase of external Ca2+ concentration. In conclusion, BV rather selectively increases the cranial and coronary blood flow. The vasodilative effects of BV seem to involve an inhibition of depolarization dependent Ca2+ slow channel. A major metabolite of BV, BVA, is inactive.