Cardiovascular effects of three calcium entry blockers in conscious dogs.

The cardiovascular effects of N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl-N-methyl-m-dithiane-2- propylamine-1,1,3,3-tetraoxide HCl (tiapamil, Ro 11-1781, Larocord), a new calcium entry blocker, were investigated in chronically-instrumented conscious dogs and compared with those of verapamil and nifedipine. Oral administration of tiapamil to normotensive dogs dilated preferentially the arterial vascular bed as evidenced by marked increases in the coronary and abdominal aortic blood flow in the absence of a depression of the myocardial contractile force. The vasodilator effects induced a reflex increase in heart rate and cardiac output, which prevented a decrease in blood pressure in normotensive, but not in renal hypertensive dogs.

Studies on the mechanism of positive inotropic activity of Ro 13-6438, a structurally novel cardiotonic agent with vasodilating properties.

We investigated the possible mechanisms involved in the positive inotropic activity of Ro 13-6438 (R-6-chloro-1,5-dihydro-3- methylimidazo -[2,1-b] quinazolin -2[ 3H]-one), a structurally novel cardiotonic agent with vasodilating properties. The positive inotropic response to Ro 13-6438 of the isolated guinea pig papillary muscle was accompanied by inhibition of myocardial phosphodiesterase (PDE) activity and elevation of intracellular cyclic AMP (cAMP) levels Ro 13-6438 had no effect on Na+,K+-stimulated or Ca2+-stimulated ATPase activity and did not influence the rate of 45Ca uptake in cardiac membrane vesicles. Ro 13-6438 caused a concentration-dependent increase in the upstroke velocity, overshoot, and duration of slow action potentials evoked in partially depolarized papillary muscles.

Cardiovascular profile of Ro 13-6438, a novel positive inotropic agent with vasodilating properties.

The cardiovascular properties of Ro 13-6438 (R-6-chloro-1,5-dihydro-3- methylimidazo -[2,1-b] quinazolin -2[ 3H]-one), a novel nonglycoside , noncatechol cardiotonic agent, were investigated in vitro and in vivo by both intravenous and oral administration. Ro 13-6438 increased tension development of isolated guinea pig left atria in a concentration-dependent manner with an EC50 of 30 microM, but had no stimulant effect on the spontaneous rate of right atria. The positive inotropic effect of Ro 13-6438 was additive to that of ouabain (0.