Nitric oxide-mediated modulation of the endothelin-1 signalling pathway in the human cardiovascular system

摘要

We studied the ability of nitric oxide(NO)to physiologically antagonize endothelin-1(ET-1) induced constrictions in human internal mannary arter(IMA). We also investigated the hypothesis that NO interacts directly with ET-receptor binding in human heart and aorta. ET-1 potently contracted IMA(EC_50 6.86 nM, 95/100 CI: 3.5-13.4 nM; n = 12). The constrictor Response to 10 nM ET-1 was fully reversed by the NO-donor diethylamine NONOate (DAE/NO; EC_50 2.0μM, 95/100 CI: 0.8-4.8μM; n = 5). The guanylate cyclase inhibitor ODQ(100μM)reduced The response to DEA/NO but did no abolish it(E)MAX 50.9±8.5/100 in the presence of ODQ; 113.0±8.4/100, control).