Cardiovascular effects of bucindolol (MJ 13105) in conscious dogs

Bucindolol (MJ 13105), administered to conscious, normotensive dogs (a) attenuated the positive chronotropic and diastolic depressor response elicited by isoproterenol, (b) increased heart rate and (c) elevated plasma renin activity (PRA). Repeated daily administration of bucindolol caused a cumulative reduction in isoproterenol-elicited cardiac and vascular responses. The increase in heart rate was not blocked by atropine and only partially attenuated by propranolol. To study the effect of bucindolol on erect blood pressure, dogs were tilted rapidly through 90 degrees from the supine to a head-up erect position, a maneuver that reflexly increases blood pressure. Following the administration of bucindolol, blood pressure in the erect position was lower than before drug but was still higher than blood pressure in the supine position suggesting the compensatory reflex response to this postural change is still functional. Bucindolol had no significant effect on P wave and QRS durations or P-R and corrected Q-T intervals of the EKG.