Effect of exercise‐training on EDHF‐mediated relaxation after chronic coronary occlusion

Abstract

Endothelium‐derived hyperpolarizing factors (EDHF) play an important role in maintaining vasodilatory capacity when nitric oxide bioavailability is impaired such as in coronary artery disease. We hypothesized that exercise training would increase the contribution of EDHF to endothelium‐dependent relaxation in coronary arteries from a model of ischemic heart disease. Ameroid constrictors were surgically placed around the proximal left circumflex coronary artery (LCX) of adult female Yucatan miniswine. Coronary rings (~1 mm luminal diameter) were isolated from the collateral‐dependent (LCX) and control (nonoccluded left anterior descending, LAD) arteries of sedentary (SED, pen confined) and exercise trained (EX, treadmill run; 5 days/wk for 14 wks) pigs. NOS inhibition (L‐NAME) attenuated bradykinin‐mediated relaxation to a greater extent in SED compared with EX of both LAD and LCX. Combined inhibition of NOS and prostanoids (indomethacin) partially corrected the EX‐enhanced relaxation observed after NOS inhibition alone, while concurrent inhibition of large‐conductance potassium (BKca) channels (iberiotoxin) ablated the differences. Thus the contribution of endothelium‐derived vasodilators is altered by EX in the underlying setting of ischemic heart disease, with an increased contribution of an EDHF acting via BKca channel, however, the specific EDHF remains undetermined. NIH:HL064931