Resistin Impairs Canine Coronary Endothelial Function through Effects on the Cyclooxygenase (COX) Pathway

Adipokines are associated with obesity, endothelial dysfunction, and coronary heart disease. Little is known about coronary vascular effects of resistin, but it has been linked to superoxide (O 2 − ). We examined mechanisms by which resistin affects coronary endothelial function. Resistin had no direct effect on coronary flow at plasma concentrations ranging from 3.0 ± 0.2 to 195 ± 24 ng/ml, nor did it affect coronary flow responses to acetylcholine (ACh; mediated largely by NO). Resistin (10–40 ng/ml) had no effect on ACh‐induced relaxation of arteries, but impaired relaxation to bradykinin (mediated by NO, EDHF, and prostaglandins). The –log EC 50 and maximum relaxation were 8.0 ± 0.1 / 99 ± 1% vs. 7.5 ± 0.1 / 96 ± 1% with and without resistin. Similarly, resistin attenuated vasodilation to bradykinin in vivo . Dihydroethidium (DHE) fluorescence, an indicator of O 2 − production, was unaltered by resistin. In contrast, pyrogallol (20 μM; a source of O 2 − ) increased Tempol‐sensitive DHE fluorescence and inhibited both ACh‐ and bradykinin‐induced relaxation. L‐NAME (100 μM) shifted bradykinin‐induced relaxation to the right (7.6 ± 0.1 / 90 ± 1%); however, resistin further inhibited relaxation (6.9 ± 0.1 / 89 ± 1%). Indomethacin (10 μM), a COX inhibitor, further inhibited bradykinin‐induced relaxation and abolished the effect of resistin (7.0 ± 0.1 / 70 ± 5% vs. 7.2 ± 0.1 / 68 ± 5%). Resistin specifically attenuates vasodilation to bradykinin. This endothelial dysfunction is neither generalized nor associated with O 2 − production, but likely involves inhibition of COX or smooth muscle responses to COX products.