Role of adenosine in noradrenergic neurotransmission during hemorrhagic hypotension.
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.
Jackson
E K
EK
Center for Clinical Pharmacology, University of Pittsburgh Medical Center, Pennsylvania.
Herzer
W A
WA
Kuan
C J
CJ
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D006470:Hemorrhage / Q000150:complications / Q000378:metabolism*; D007022:Hypotension / Q000209:etiology / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D009435:Synaptic Transmission; D014970:Xanthines / Q000494:pharmacology*
D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; D012083:Renin; D000241:Adenosine; D009638:Norepinephrine