Extravascular adenosine influences endothelium-derived nitric oxide release from perfused dog semitendinosus artery.
We tested the hypothesis that extravascular adenosine induces the release of vasodilatory products from endothelial cells lining skeletal muscle vessels. Endothelium-intact (n = 35) and -denuded (n = 5) dog semitendinosus intramuscular arteries were isolated, cannulated, and placed in 100-mL baths containing Krebs-Henseleit bicarbonate buffer (Krebs) at 37 degrees C and gassed with 95% O2--5% CO2. Each vessel, as well as a parallel tubing segment (avascular control), was perfused at 3.5 +/- 0.2 mL/min (inflow pressure 94 +/- 2 mmHg; 1 mmHg = 133.3 Pa) with Krebs containing 100 microM phenylephrine, 6% dextran, and 15 units/mL superoxide dismutase. Perfusate from all segments dripped onto endothelium-denuded dog femoral artery rings. The addition of 10 microM acetylcholine to the perfusate to test the functional integrity of endothelium-intact donor segments did not alter resistance in vessel segments or change force in rings. The addition of 100 microM adenosine to the extravascular bath decreased resistance 1.5 +/- 0.4 mmHg.mL-1.min-1 in vessel segments but was without effect on downstream rings. When acetylcholine was retested in the presence of extravascular adenosine, a relaxation (16 +/- 6%) occurred in rings receiving perfusate from endothelium-intact segments but not endothelium-denuded or tubing segments. This relaxation was eliminated by N omega-nitro-L-arginine (10 microM), a nitric oxide synthase inhibitor, and was attenuated to 4 +/- 1% by 8-phenyltheophylline (10 microM), an adenosine receptor antagonist. Thus adenosine, in conjunction with acetylcholine, acting through a receptor-mediated event, resulted in the release of nitric oxide from the endothelium of perfused intramuscular arteries, indicating the potential for extravascular conditions to influence the release of endothelium-derived products.
Woodley
N
N
Department of Human Biology and Nutritional Sciences, University of Guelph, ON, Canada.
Barclay
J K
JK
D000109:Acetylcholine; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010477:Perfusion
D002317:Cardiovascular Agents; D009569:Nitric Oxide; D000241:Adenosine; D000109:Acetylcholine