Reflex bradycardia induced by hydralazine in sino-aortic deafferented conscious rats.
1. It is generally recognized that the vasodilator hydralazine produces hypotension accompanied by baroreflex-mediated tachycardia. In some experimental conditions, however, the accompanying heart rate change is bradycardia, a paradoxical response which has not been satisfactorily explained. The present study examined the possibility of hydralazine-induced bradycardia being mediated by vagal or sympathetic afferents activated by changes in left ventricular pressure. 2. Systolic blood pressure and heart rate responses to hydralazine were recorded in conscious normotensive intact rats by a tail cuff method and compared with responses in animals subjected to previous sino-aortic deafferentation (SAD) to remove the influence of the arterial baroreflex. Responses were also obtained after blockade of myocardial afferent vagal C-fibres with urethane, of efferent vagal impulses to the heart with methylatropine, of positive inotropic effects of hydralazine with atenolol, and of prostanoid sensitization of myocardial nerve fibres with indomethacin. 3. Hydralazine produced hypotension and tachycardia in intact rats, and hypotension and bradycardia in SAD animals. In intact rats, this pattern was not affected by any of the pretreatments, while in SAD rats, all pretreatments reversed the bradycardia to hydralazine. 4. The present results indicate that suppression of the arterial baroreflex by SAD propitiates the appearance of a bradycardiac response to hydralazine. This reaction probably results from activation of a vagal cardiodepressant reflex originating in the heart, as suggested by its blockade by drugs acting at various sites along the reflex arch.
Sánchez-Salvatori
M A
MA
Department of Pharmacology, School of Medicine, Universidad Nacional Autónoma de México, Apartado Postal 70297, 04510 Mexico, DF, Mexico.
Vidrio
H
H
D000818:Animals; D001011:Aorta / Q000502:physiology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia / Q000139:chemically induced / Q000503:physiopathology*; D002346:Carotid Sinus / Q000187:drug effects* / Q000294:innervation* / Q000502:physiology; D003243:Consciousness / Q000187:drug effects* / Q000502:physiology; D003714:Denervation; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006830:Hydralazine / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D006830:Hydralazine