Cardiovascular profile of Bay K 8644, a presumed calcium channel activator, in the dog.

Abstract

Bay k 8644, although belonging to dihydropyridines, has been reported to exert effects directionally opposite to those of dihydropyridine calcium channel blockers such as nifedipine. The present experiments were carried out to elucidate whether this is indeed true. All experiments were done on isolated, blood-perfused dog-heart preparations described below, and Bay k 8644 was administered intra-arterially. In sinoatrial (SA) node preparations Bay k 8644 increased sinus rate by about 37% of the basal value at the highest dose (10 micrograms). In atrioventricular (AV) node preparations Bay k 8644 decreased AV conduction time by accelerating AV nodal but not intraventricular conduction. However, the decrease in AV conduction time remained at about 10 ms (about 7.8% of the basal value) even at the highest dose (10 micrograms). In papillary muscle preparations driven at a fixed rate of 120 stimuli/min Bay k 8644 increased the force of contraction by about 100% of the basal value at the highest dose (10 micrograms). In spontaneously beating papillary muscle preparations Bay k 8644 failed to increase the rate of automaticity although it increased the force of contraction. In all preparations Bay k 8644 decreased (coronary) blood flow down to about 20% of the basal value at the highest dose (10 micrograms). The positive chronotropic and dromotropic effects of Bay k 8644 reached respective peaks nearly at the same time as its vasoconstrictor effect, whereas its positive inotropic effect reached a peak after the vasoconstrictor effect had nearly worn off.(ABSTRACT TRUNCATED AT 250 WORDS)