Evidence that 5-MT3 receptors in the nucleus tractus solitarius and other brainstem areas modulate the vagal bradycardia evoked by activation of the von Bezold-Jarisch reflex in the anesthetized rat

The effects of intracisternal (i.c.) application of the 5-HT3 receptor antagonist granisetron (0.016-0.16 mu g kg(-1)) and the agonist phenylbiguanide (0.3-3 mu g kg(-1)) on reflex bradycardia evoked by injection of phenylbiguanide (i.v.; 10 mu g kg(-1)) were investigated in urethane anesthetized atenolol-pretreated rats. The effect of bilateral microinjection of granisetron (10 nmol per side, 100 nl) into the nucleus tractus solitarius (NTS) on the reflex was also investigated. Intracisternal administration of granisetron dose-dependently (0.016-0.16 pg kg(-1)) and significantly attenuated the reflex bradycardia whilst the highest dose given i.v. had no significant effect on the reflex bradycardia. Phenylbiguanide given i.c. only caused significant potentiation at the middle dose (1 mu g kg(-1)), having no significant effects at the other doses. Neither granisetron nor phenylbiguanide given i.c. affected resting heart rate or blood pressure. Granisetron microinjected bilaterally into the NTS also significantly attenuated both reflex bradycardia and hypotension. It is concluded that excitation of cardiac vagal motoneurones evoked by cardiopulmonary afferents involves activation of 5-HT3 receptors located in the nucleus tractus solitarius and other brainstem areas. (C) 1998 Elsevier Science B.V.