title: 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.
authors.affiliation: Département de Pharmacologie, Faculté de Médecine, Le Kremlin-Bicêtre, France.
authors.forename: E
authors.initials: E
authors.lastname: Scalbert
authors.forename: C
authors.initials: C
authors.lastname: Richer
authors.forename: J F
authors.initials: JF
authors.lastname: Giudicelli
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D009411:Nerve Endings / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects
chemical_list: D007650:Ketanserin; D011188:Potassium