ROLE OF ADENOSINE IN NORADRENERGIC NEUROTRANSMISSION DURING HEMORRHAGIC HYPOTENSION

The purpose of this study was to test the hypothesis that endogenous a denosine suppresses noradrenergic neurotransmission during hemorrhagic hypotension. Rats were prepared for in situ blood-perfusion of their mesenteric vascular beds and received throughout the protocol an intra mesenteric artery infusion of either saline (n =14) or 1,3-dipropyl-8- (p-sulfophenyl)xanthine (DPSPX, 40 mu g/min; n = 14), an adenosine rec eptor antagonist. Vascular responses to periarterial sympathetic nerve stimulation (PNS; 3, 5 and 7 Hz) and to exogenous norepinephrine (NE; 100, 200 and 300 ng) were obtained at base-line and at 30, 75 and 120 min into hemorrhagic hypotension (arterial blood pressure = 50 mm Hg) . Some experiments were conducted in rats without kidneys to prevent i ndirect modulation of neurotransmission by adenosine via the renin-ang iotensin system. Vascular responses to PNS and NE were not significant ly affected by DPSPX regardless of time into hemorrhagic hypotension, presence or absence of kidneys or stimulus intensity frequency of PNS or dose of NE). Hemorrhagic hypotension per se significantly (P <.0001 ) potentiated responses to PNS but did not significantly affect respon ses to NE. The effect of hemorrhage on responses to PNS was not signif icantly affected by DPSPX or nephrectomy and occurred similarly at all three levels of PNS. During hemorrhage, DPSPX treatment significantly increased PRA levels (P <.039) in rats with intact kidneys. These dat a indicate that endogenous adenosine inhibits renin release during hem orrhagic hypotension, but does not attenuate noradrenergic neurotransm ission even during prolonged hemorhagic hypotension. Finally, these ex periments indicate that hemorrhagic hypotension can enhance noradrener gic neurotransmission by a mechanism that does not involve the renal r eninangiotensin system.