Interaction between the cardiovascular effects of clonidine and the kappa-opioid agonist U-50,488H in the anterior hypothalamic area of the rat brain.

Abstract

In thiobutabarbitone-anaesthetized rats, microinjection of clonidine (1-40 nmol) into the anterior hypothalamic area (AHy) produced dose-dependent reductions in mean arterial blood pressure and heart rate. Microinjection of the kappa-opioid agonist U-50,488H (3 and 10 nmol) did not modify these parameters. Simultaneous co-administration of clonidine (4 nmol) and U-50,488H (10 nmol) into the AHy resulted in significant potentiation of the clonidine-induced hypotension and marked attenuation of the bradycardia. A lower dose of U-50,488H (3 nmol) co-administered with clonidine (4 nmol) did not influence the cardiovascular responses to clonidine. These findings suggest that AHy neurons involved in the cardiovascular responses to clonidine may be modulated by kappa-opioid receptor stimulation.