Role of nitric oxide in hypoxic coronary vasodilatation in isolated perfused guinea pig heart.
To test the hypothesis that nitric oxide (NO) mediates hypoxic coronary dilatation in situ, isolated guinea pig hearts were perfused at constant pressure (Langendorff technique) with physiological salt solution. Switching from a control perfusate (95% O2-5% CO2) to one equilibrated with a lower O2 tension (20% O2) induced a large, but submaximal and reproducible, coronary dilatation. The NO synthase inhibitor NG-nitro-L-arginine (L-NNA) diminished baseline flow (3.67 +/- 0.24 vs. control 5.11 +/- 0.42 ml.min-1 x g-1; P < 0.05) and selectively blocked the coronary flow response to acetylcholine without reducing the response to papaverine. L-NNA reduced the absolute increase in coronary flow during hypoxia by 27 +/- 2% (delta flow = 5.83 +/- 0.49 vs. control delta flow = 8.04 +/- 0.74 ml.min-1 x g-1; P < 0.05). Hypoxic coronary dilatation was unaffected by infusion of the thromboxane mimetic U-46619, which decreased baseline coronary flow to the same extent as L-NNA. Prior addition of indomethacin did not alter the attenuating effect of L-NNA. Hypoxic coronary dilatation during constant flow perfusion at 14.7 +/- 0.28 ml/min was reduced by 65 +/- 5% after L-NNA. Therefore, the NO component of the response was not a consequence of the reduced baseline flow observed in the presence of L-NNA, did not depend on prostaglandin synthesis, and was not secondary to increased flow or intravascular shear stress. We conclude that hypoxic coronary vasodilatation in isolated guinea pig hearts is partially mediated by NO.
Brown
I P
IP
Department of Physiology, New York Medical College, Valhalla 10595.
Thompson
C I
CI
Belloni
F L
FL
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D010100:Oxygen / Q000008:administration & dosage; D010208:Papaverine / Q000494:pharmacology; D010477:Perfusion; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*
D011450:Prostaglandin Endoperoxides, Synthetic; D019335:Nitroarginine; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D010208:Papaverine; D000109:Acetylcholine; D010100:Oxygen; D007213:Indomethacin