Roles of the central prostaglandin EP3 receptors in cardiovascular regulation in rats

In this study, we examined the effects of an intracerebroventricular (i.c.v.) administration of prostaglandin E-2 (PGE(2)) and of selective agonists for PGE(2) receptor subtypes, EP1, EP2, EP3 and EP4, on central cardiovascular regulation and renal sympathetic nerve activity (RSNA) in urethane-anesthetized rats. The central administration of PGE(2) (0.01-1.0 nmol) resulted in increases in blood pressure, heart rate (HR) and RSNA in a dose-dependent manner. Cardiovascular responses to PGE(2) (0.5 nmol, i.c.v.) were attenuated by pretreatment with ganglionic and adrenoceptor blocking agents, but not with SC-19220 (20 nmol, i.c.v.), an EP1 receptor antagonist. An i.c.v. administration of the EP3 agonist ONO-AE-248 (50.0 nmol) resulted in an increase in RSNA with pressor and tachycardia responses, while administration of the EP2 agonist ONO-AE1-259 and the EP4 agonist ONO-AE1-329 caused transient hypotension and slight increases in HR and RSNA. The administration of the selective EP1 agonist ONO-DI-004 showed no effect. These results suggest that the central PGE(2)-induced activation of the sympathetic nerve activity with hypertension and tachycardia may depend on stimulation of the EP3 receptors in the central nervous system. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.