The purpose of this study was to test the hypothesis that endogenous
adenosine 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 intramesenteric artery infusion of either saline (n = 14) or 1,3-dipropyl-8-(p-sulfophenyl)-xanthine (
DPSPX, 40 micrograms/min; n = 14), an
adenosine receptor 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 indirect modulation of neurotransmission by
adenosine via the renin-angiotensin system. Vascular responses to PNS and NE were not significantly 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 responses to NE. The effect of
hemorrhage on responses to PNS was not significantly 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 data indicate that endogenous
adenosine inhibits
renin release during hemorrhagic
hypotension, but does not attenuate noradrenergic neurotransmission even during prolonged hemorrhagic
hypotension. Finally, these experiments indicate that hemorrhagic
hypotension can enhance noradrenergic neurotransmission by a mechanism that does not involve the renal renin-angiotensin system.