Physiological antagonism of endothelin-1 in human conductance and resistance coronary artery

1 The ability of four endogenous vasodilators, nitric oxide (NO; 0.01 - 30 muM), atrial (ANP), brain (BNP) and C-type (CNP) natriuretic peptide (0.1 3 00 nM). to reverse endothelin-1 (ET-1; 10 nM) constrictions in human resist ance and conductance coronary arteries (CA) in vitro was investigated. 2 ET-1 (0.1 - 300 nM) constricted resistance CA more potently than conducta nce CA (P<0.05: EC50 values 2.98 nM (95% CI: 1.49 - 5.95 nM and 8.58 (4.72 - 15.6 nM) respectively)). 3 The NO-donor diethylamine NONOate fully reversed the ET-1 constriction in conductance CA (E-MAX 127+/-9.16%), however only partial reversal was obse rved in resistance CA (E-MAX 78.8+/-8.13; P<0.05). The soluble guanylate cy clase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]qUinoxalin-1-one (100 muM) reduc ed the maximum response to diethylamine NONOate to 76.9+/-14.4% in conducta nce CA (P<0.05), but had no effect on resistance CA (E-MAX 77.2+/-18.4%). 4 There was no difference between responses to ANP in conductunce and resis tance CA (EC50 values 4.25 nM (0.84 - 21.4 nM) and 18.4 nM (2.92 116 nM), E -MAX 53.1+/-14.7% and 48.6+/-11.8% respectively). 5 BNP was a more potent vasodilator of conductance than resistance CA. In c onductance CA the mean EC50 value was 2.4 nM (0.74 - 7.75 nM). E-MAX 54.5+/ -14.9%. Concentration-response curves to BNP were incomplete in resistance CA. 6 Concentration-response curves to CNP were incomplete in both conductunce and resistance CA. 7 The greater potency of ET-1 in resistance vessels may exacerbate the effe cts of increased circulating levels of the peptide in disease. Only NO coul d fully reverse ET-1 medicated constrictions in conductance CA, and none of the dilators tested could completely counteract constrictions in resistanc e CA.