Reduced PO2 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 fa ll in arteriolar wall PO2 may be a stimulus for the sustained release of en dothelial nitric oxide (NO) during sympathetic vasoconstriction in the supe rfused rat intestine. In this study, we tested the hypothesis that locally formed adenosine serves as the link between the fall in local PO2 and NO sy nthesis under these conditions. Adenosine applied via pressurized micropipe ttes directly onto the wall or at a distance of 25 mum from the wall of fir st-order arterioles (resting diameter = 54 +/- 1 mum) elicited dose-depende nt dilations of 15-46% that were significantly reduced by the NO synthase i nhibitor N-G-monomethyl-L-arginine (L-NNMA, 10(-4) M). Arteriolar responses to sympathetic nerve stimulation were enhanced by 57-66% in the presence o f L-NMMA or when tissue PO2 was prevented from falling under a high O-2 sup erfusate. Adenosine deaminase (2.0 U/ml) or the selective Al receptor antag onist 8-cyclopentyl-1,3-dipropylxanthine (3 x 10(-4) M) completely blocked the enhancing effect of L-NMMA on sympathetic constriction. These results a re consistent with the hypothesis that the fall in arteriolar wall and/or t issue PO2 that accompanies sympathetic arteriolar constriction in the rat i ntestine can lead to local adenosine production, which in turn preserves en dothelial NO release. Copyright (C) 2001 S. Karger AG, Basel.