Comparison of two substances with a possible alpha-adrenoceptor blocking and calcium channel blocking activity in rabbits in vivo under the paced and non-paced heart conditions. I. The effects on cardiac contractility (left ventricular dP/dtmax.).

The effects of substances--which in the isolated preparations possess calcium channel and alpha-adrenoceptor blocking activity--on cardiac contractility (dP/dtmax. of the blood pressure in the left ventricle) were evaluated. Substances VUFB 17951 (0.046 and 0.46 mg/kg) and VUFB 17959 (0.045 and 0.45 mg/kg) were administered intravenously in rabbits in vivo in pentobarbital anaesthesia under the conditions of the paced and non-paced heart rate. VUFB 17951 induced dose-dependent, immediately after the administration onsetting, progressive and significant decrease in dP/dtmax. (max. 50.5% in the paced and 51.4% in the non-paced heart). The effects of substance VUFB 17959 were less marked. On the basis of the results obtained in the present study it is possible to consider the participation of more mechanisms of the action (inc. calcium-channel antagonistic ones) related to negative inotropic effects of the substances. The absence of significant differences in the reaction of dP/dtmax. between the paced and non-paced heart conditions may then indicate a presence of a direct cardiodepressant action of substances VUFB 17951 and 17959.