Lack of presynaptic effects of ketanserin on cardiac noradrenergic nerve terminals in the SHR.

Abstract

The potential cardiac presynaptic effects of ketanserin (K) (0.01-3.00 mg/kg IV) were investigated in pithed SHR in 4 experimental conditions: (a) basal heart rate (HR); (b) HR increased by selective cardiac sympathetic stimulation (SS); (c) HR increased by aminophylline infusion; and (d) HR increased by SS and brought back to basal value by clonidine. Control groups were treated with saline. In the 4 types of experiments, K, starting from 0.3 mg/kg, induced almost identical and dose-dependent decreases in HR (maximal reduction: 45 beats/(min at 3 mg/kg). Thus we conclude: (1) that K is devoid of any presynaptic facilitatory effect on norepinephrine release since it was unable to raise HR in experiment D; (2) that K is devoid of any presynaptic inhibitory effect on norepinephrine release since it lowered HR to the same extent in both experiments B (noradrenergic tachycardia) and (non-noradrenergic tachycardia); and C (3) that the bradycardia which was induced by high doses of K (much above those required to block 5-HT2 and alpha 1-adrenergic receptors) and which was of similar magnitude in the 4 experimental conditions is probably due to a direct, nonspecific depressant effect of K on the sinus node.