1983 Volume 81 Issue 1 Pages 39-58
Cardiovascular actions of guanabenz, a new antihypertensive agent, were studied in comparison with those of clonidine and guanethidine. Guanabenz, administered intravenously, produced a rise of blood pressure which was followed by a prolonged fall in anesthetized dogs. Guanabenz also decreased the heart rate, inhibited the respiration, and produced an alteration in T wave and a prolongation of PQ or TP interval in the ECG of the dog. Such effects of guanabenz on blood pressure and heart rate were observed in the cat, rabbit and rat, but there was a slight species-difference in the effects. Clonidine, but not guanethidine, produced responses similar to those of guanabenz. The potency of guanabenz to produce hypotension and bradycardia was approximately 1/10 that of clonidine and 10 times higher than that of guanethidine. The depressor effect of guanabenz was not observed in the spinal cats; thus, the blood pressure rose after the administration. When guanabenz was administered intracerebroventricularly or into the nucleus tractus solitarius of rats, the initial pressor response was not produced, and the depressor and bradycardiac responses were observed. Guanabenz, administered intravenously or intra-arterially, produced an inhibition of cardiac functions, decreased the blood flow of common carotid and femoral arteries, and elevated the perfusion-pressure of the hindlimb in the dog. In the isolated rabbit and guinea-pig atria, guanabenz produced negative inotropic and chronotropic effects and attenuated the rate of rise of the action potential. The contractile responses to serotonin and histamine in the isolated rabbit thoracic aorta were noncompetitively inhibited by guanabenz. From these results, it is suggested that the hypotensive and bradycardiac actions of guanabenz are mediated via central actions, as well as those of clonidine. Furthermore, in addition to the central actions, it was found that guanabenz acts directly on cardiovascular tissues and attenuates the responsiveness.
