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Shear stress-induced nitric oxide antagonizes adenosine effects on intestinal metabolism
1Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0W3.
Abstract:
The influence of nitric oxide (NO) on adenosine-induced metabolic effects was studied in the intestine. Blood flow supplied an in situ- isolated segment of small intestine in anesthetized cats via the superior mesenteric artery (SMA) and was controlled by a vascular circuit. The SMA and portal samples were taken for analysis of oxygen and lactate. Adenosine (0.4 mg. kg-1. min-1, intra-SMA) reduced oxygen consumption by 25.1 +/- 2.9 from 73.1 +/- 10.8 micromol. min-1. 100 g-1 and increased lactate production by 13.3 +/- 3.0 from 12.8 +/- 4.6 micromol. min-1. 100 g tissue-1 during constant-flow (CF, decreased shear stress) but not during constant-pressure (CP, increased shear stress) perfusion. Blockade of NO synthase using Nomega-nitro-L-arginine methyl ester did not affect the metabolic effects of adenosine during CF but eliminated the differences seen between CP and CF perfusion. A NO donor, 3-morpholinosydnonimine, attenuated the metabolic effects of adenosine during CF perfusion. The results suggested that shear-induced NO antagonized metabolic effects of adenosine but that the inhibition of vascular effects by NO was not shear dependent since it occurred in both CP and CF perfusion.
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