Date of Graduation
School of Medicine
Physiology, Pharmacology & Neuroscience
Matthew A. Boegehold.
Despite a profound reduction in hemodynamic shear stress, a sustained release of endothelium-derived nitric oxide (NO) limits arteriolar constriction during periods of increased sympathetic nerve activity in the rat small intestine. In this project, we sought to test the hypothesis that adenosine, formed in response to a flow-dependent fall in local PO2, serves as the stimulus to preserve endothelial NO release under these conditions. Sympathetic nerve stimulation induced frequency-dependent arteriolar constrictions and a flow-dependent fall in local PO2. The arteriolar responses to nerve stimulation were enhanced after inhibition of NO synthase with NG-monomethyl-L-arginine (L-NMMA). Under a high (20%) O2 superfusate, the fall in local PO2 during nerve stimulation was significantly attenuated, arteriolar constrictions were significantly increased, and these responses were no longer sensitive to L-NMMA. Treatment with adenosine deaminase (2.0 U/ml) or the selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (4 x 10-4 M) completely blocked the enhancing effect of L-NMMA on sympathetic constriction. In the presence of the 5'-ectonucleotidase inhibitor alpha,beta-methyleneadenosine 5'-diphosphate (4.5 x 10-5 M), the enhancing effects of L-NMMA and the high-O2 superfusate on sympathetic constriction were preserved. None of these treatments had an effect on vascular smooth muscle responsiveness to NO (as judged by arteriolar responses to sodium nitroprusside). The high-O 2 superfusate also did not lead to the generation of reactive oxygen species in the arteriolar wall (as determined by the reduction of tetranitroblue tetrazolium dye). In conclusion, these results suggest that a flow-dependent fall in arteriolar wall and/or tissue PO2 leads to the release of intracellularly-formed adenosine, which, through its interaction with endothelial A1 receptors, stimulates NO release during neurogenic constriction in this vascular bed.
Sauls, Bryan Auston, "Integrated modulation of sympathetic tone in the microcirculation by oxygen, adenosine, and nitric oxide" (2001). Graduate Theses, Dissertations, and Problem Reports. 1409.