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

Abstract 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.