Reduced PO(2) and adenosine formation preserve arteriolar nitric oxide synthesis during sympathetic constriction in the rat intestine.
Previous reports by this laboratory have indicated that a flow-dependent fall in arteriolar wall PO(2 )may be a stimulus for the sustained release of endothelial nitric oxide (NO) during sympathetic vasoconstriction in the superfused rat intestine. In this study, we tested the hypothesis that locally formed adenosine serves as the link between the fall in local PO(2) and NO synthesis under these conditions. Adenosine applied via pressurized micropipettes directly onto the wall or at a distance of 25 microm from the wall of first-order arterioles (resting diameter = 54 +/- 1 microm) elicited dose-dependent dilations of 15-46% that were significantly reduced by the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 10(-4) M). Arteriolar responses to sympathetic nerve stimulation were enhanced by 57-66% in the presence of L-NMMA or when tissue PO(2) was prevented from falling under a high O(2) superfusate. Adenosine deaminase (2.0 U/ml) or the selective A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (4 x 10(-4) M) completely blocked the enhancing effect of L-NMMA on sympathetic constriction. These results are consistent with the hypothesis that the fall in arteriolar wall and/or tissue PO(2) that accompanies sympathetic arteriolar constriction in the rat intestine can lead to local adenosine production, which in turn preserves endothelial NO release.
Sauls
B A
BA
Department of Physiology, West Virginia University School of Medicine, Morgantown, W. Va., USA.
Boegehold
M A
MA
D000241:Adenosine / Q000096:biosynthesis*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000201:enzymology / Q000294:innervation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000098:blood supply / Q000201:enzymology* / Q000294:innervation; D008297:Male; D008839:Microelectrodes; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D010313:Partial Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014970:Xanthines; D019323:omega-N-Methylarginine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D019001:Nitric Oxide Synthase; D000243:Adenosine Deaminase; D000241:Adenosine; D010100:Oxygen