Adenosine linking reduced O2 to arteriolar NO release in intestine is not formed from extracellular ATP.

We have previously reported that adenosine formed in response to reduced arteriolar and/or tissue PO(2) preserves endothelial nitric oxide (NO) synthesis during sympathetic vasoconstriction in the rat intestine. To more precisely identify the site and mechanism of adenosine formation under these conditions, we tested the hypothesis that ATP released in response to reduced O(2) levels serves as a source of adenosine. Direct application of ATP to the wall of first-order arterioles elicited dose-dependent dilations of 15-33% above resting diameter that were reduced by 71-80% by the 5'-ectonucleotidase inhibitor alpha,beta-methyleneadenosine 5'-diphosphate (AOPCP, 4.5 x 10(-5) M) and completely abolished by N(G)-monomethyl-L-arginine (L-NMMA, 10(-4) M). Under control conditions, sympathetic nerve stimulation at 3 and 8 Hz induced arteriolar constrictions of 11 +/- 1 and 19 +/- 1 microm, respectively. These responses were enhanced by 58-69% in the presence of L-NMMA or when local PO(2) was maintained at resting levels. However, in the presence of AOPCP, the enhancing effects of L-NMMA and the high O(2) superfusate on sympathetic constriction were preserved. These results suggest that, although exogenously applied ATP can stimulate arteriolar NO release in the intestine largely through its sequential extracellular hydrolysis to adenosine, this process does not contribute to adenosine formation and sustained NO release during sympathetic constriction in this vascular bed.