Different activation of L-arginine pathway by bradykinin, serotonin, and clonidine in coronary arteries.
Endothelial cells release nitric oxide from L-arginine, and this pathway can be inhibited by the analogue of L-arginine, NG-monomethyl-L-arginine (L-NMMA). The effect of L-NMMA on endothelium-dependent relaxation of epicardial porcine coronary arteries was studied in isolated blood vessels suspended in organ chambers for isometric tension recording. Endothelium-dependent relaxations to bradykinin, serotonin, and the alpha 2-adrenergic agonist clonidine were evaluated in the presence and absence of L-NMMA (10(-5)-10(-3) M). L-NMMA, as well as the inhibitor of guanylate cyclase methylene blue (10(-5) M) and hemoglobin (10(-5) M), inhibited endothelium-dependent relaxation to serotonin and clonidine. The effect of L-NMMA could be reversed by L-arginine but not by D-arginine. In contrast, L-NMMA, methylene blue, and hemoglobin caused a weak inhibition of the endothelium-dependent relaxation evoked by bradykinin; indomethacin and tranylcypromine had no effect. The inhibitor of Gi proteins pertussis toxin (100 ng/ml) abolished the relaxations evoked by clonidine and markedly reduced those evoked by serotonin but did not affect those caused by bradykinin. In the presence of pertussis toxin, L-NMMA induced a further reduction of the relaxations to serotonin, suggesting that inhibition of Gi proteins does not completely prevent the activation of the L-arginine pathway. Thus endothelium-dependent relaxations to serotonin and to the alpha 2-adrenergic agonist clonidine are mediated through the release of nitric oxide formed from L-arginine in endothelial cells, whereas bradykinin evokes endothelium-dependent relaxations via a different pathway.
Richard
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V
Department of Research, University Hospital, Basel, Switzerland.
Tanner
F C
FC
Tschudi
M
M
Lüscher
T F
TF
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology*; D003331:Coronary Vessels / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D013552:Swine
D015221:Potassium Channels; D012701:Serotonin; D000255:Adenosine Triphosphate; D001120:Arginine; D011451:Prostaglandin-Endoperoxide Synthases; D019204:GTP-Binding Proteins; D003000:Clonidine; D001920:Bradykinin