Role of adenosine in noradrenergic neurotransmission in spontaneously hypertensive rats.
The purpose of this study was to compare the in vivo role of adenosine as a modulator of noradrenergic neurotransmission in the spontaneously hypertensive rat (SHR) and Wistar-Kyoto control rat (WKY). In the in situ blood-perfused rat mesentery, vascular responses to periarterial (sympathetic) nerve stimulation (PNS) and to exogenous norepinephrine (NE) were enhanced in SHR compared with WKY. In both SHR and WKY, vascular responses to PNS were more sensitive to inhibition by adenosine than were responses to NE. At matched base-line vascular responses, compared with WKY, SHR were less sensitive to the inhibitory effects of adenosine on vascular responses to PNS, but SHR and WKY were equally sensitive with respect to adenosine-induced inhibition of responses to NE. Antagonism of adenosine receptors with 1,3-dipropyl-8-p-sulfophenylxanthine shifted the dose-response curve to exogenous adenosine sixfold to the right yet did not influence vascular responses to PNS or NE in either SHR or WKY. Furthermore, PNS did not alter either arterial or mesenteric venous plasma levels of adenosine in SHR or WKY, and plasma levels of adenosine in both strains were always lower than the calculated threshold level required to attenuate neurotransmission. It is concluded that in vivo 1) exogenous adenosine interferes with noradrenergic neurotransmission in both SHR and WKY; 2) SHR are less sensitive to the inhibitory effects of exogenous adenosine on noradrenergic neurotransmission than are WKY; 3) endogenous adenosine does not play a role in modulating neurotransmission in either strain under the conditions of this study; and 4) enhanced noradrenergic neurotransmission in the SHR is not due to defective modulation of neurotransmission by adenosine.
Jackson
E K
EK
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006973:Hypertension / Q000503:physiopathology*; D008643:Mesentery / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects*; D014970:Xanthines / Q000494:pharmacology
D014970:Xanthines; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; D010424:Pentobarbital; D000241:Adenosine; D009638:Norepinephrine