Importance of endothelium-derived nitric oxide in porcine coronary resistance arteries.
Endothelial cells regulate vascular tone through the release of nitric oxide and other relaxing factors. The role of these substances was studied in isolated intramyocardial porcine coronary resistance arteries suspended in myographs for isometric tension recording. The inhibitor of nitric oxide formation NG-monomethyl-L-arginine (L-NMMA; 10(-7)-10(-4)M), but not D-NMMA, caused endothelium-dependent contractions that could be reversed by L-arginine but not by D-arginine. In preparations with endothelium, L-NMMA potentiated the contractions induced by acetylcholine and the relaxations to 3-morpholino-sydnonimine. Under both conditions, the effect of endothelial removal was slightly more pronounced than that of L-NMMA. Bradykinin, serotonin, and the alpha 2-adrenergic agonist clonidine evoked endothelium-dependent relaxations. L-NMMA as well as the inhibitor of guanylate cyclase methylene blue (10(-5) M) prevented the relaxations induced by clonidine, reduced those to serotonin, but hardly affected those to bradykinin. Thus, in porcine coronary resistance arteries, endothelium-derived nitric oxide is continuously produced from L-arginine. Endothelium-dependent relaxations to clonidine are fully mediated and those to serotonin partially mediated by nitric oxide; its release does not involve a Gi protein. An endothelium-derived relaxing factor different from nitric oxide must mediate the relaxations to bradykinin and contribute to those evoked by serotonin.
Tschudi
M
M
Department of Research, University Hospital, Basel, Switzerland.
Richard
V
V
Bühler
F R
FR
Lüscher
T F
TF
D000818:Animals; D001120:Arginine / Q000502:physiology; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D009569:Nitric Oxide; D012701:Serotonin; D001120:Arginine; D003000:Clonidine; D001920:Bradykinin