Shear stress-induced nitric oxide antagonizes adenosine effects on intestinal metabolism.
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.
D000241:Adenosine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity; D002415:Cats; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018056:Hemorheology; D007421:Intestine, Small / Q000098:blood supply* / Q000187:drug effects*; D019344:Lactic Acid / Q000097:blood; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000502:physiology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects