Alpha-adrenoceptor- and prostaglandin-mediated modulation of vascular adrenergic neurotransmission in spontaneously hypertensive rats.

Abstract

The modulation of vascular adrenergic neurotransmission in the spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat (WKY) mediated by alpha-adrenoceptor and prostaglandin E2 (PGE2) were evaluated. The pressor responses of the perfused mesenteric vascular bed to perivascular adrenergic nerve stimulation (NS) and infusion of norepinephrine (NE) and the NS-induced 3H-efflux in preparations pretreated with 3H-norepinephrine were determined. In both SHR and WKY, a selective alpha 2 agonist, B-HT 920 (30-300 nM), inhibited neurogenic vasoconstriction, and B-HT 920 (100-300 nM) potentiated the pressor response to NE in a dose-dependent manner. The effects of B-HT 920 did not significantly differ in SHR and WKY. Another alpha 2 agonist, clonidine (100 nM), decreased the 3H-efflux approximately by 30% both in SHR and WKY. A selective alpha 2 blocking agent, yohimbine (3-300 nM), potentiated the neurogenic vasoconstriction and inhibited the pressor response to NE equally in SHR and WKY. No difference in enhancement of 3H-efflux by yohimbine (30-300 nM) was seen between SHR and WKY either in the absence or presence of cocaine (10 microM) and metanephrine (20 microM). PGE2 (0.1-1 microM) potentiated pressor responses to NS and NE in SHR and WKY, but this compound (1 microM) did not affect the NS-induced 3H-efflux in either group of rats. It appears that adrenergic neurotransmission is inhibited presynaptically via an alpha 2 receptor mechanism and facilitated postsynaptically by PGE2 in the rat mesenteric vascular bed. The hypertensive state in SHR can not be accounted for by alteration of these modulator mechanisms.