Alpha-adrenoceptor- and prostaglandin-mediated modulation of vascular adrenergic neurotransmission in spontaneously hypertensive rats.
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.
D000818:Animals; D001338:Autonomic Fibers, Postganglionic / Q000502:physiology; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D015232:Dinoprostone; D004558:Electric Stimulation; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation*; D018377:Neurotransmitter Agents / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011458:Prostaglandins E / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D001381:Azepines; D018377:Neurotransmitter Agents; D011458:Prostaglandins E; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C024763:talipexole; D015232:Dinoprostone; D003000:Clonidine; D009638:Norepinephrine