Coronary vasodilator effects of BNP: mechanisms of action in coronary conductance and resistance arteries

Brain natriuretic peptide (BNP), a hormone secreted predominantly in ventri cular myocytes, may influence coronary vascular tone. We studied the corona ry vasodilatory response to BNP under physiological conditions and after pr econstriction with endothelin-1 (ET-1) in anesthetized pigs. Average peak-f low velocity (APV) was measured using intracoronary Doppler, and cross-sect ional area (CSA) was measured using intravascular ultrasound. Coronary bloo d flow (CBF) was calculated. Intracoronary BNP induced dose-dependent incre ases in CSA, APV, and CBF similar in magnitude to those induced by nitrogly cerin (NTG). The magnitude of BNP-induced vasodilation was accentuated afte r preconstriction with ET-1. Pretreatment with either the nitric oxide synt hase inhibitor N-omega-nitro-L-arginine methyl ester or the cyclooxygenase inhibitor indomethacin attenuated the coronary vasodilator effect of BNP in resistance arteries without influencing epicardial vasodilation. Pretreatm ent with the ATP-sensitive potassium-channel blocker glibenclamide enhanced epicardial vasodilation in response to BNP. We conclude that BNP exerts co ronary vasodilator effects, predominantly in epicardial conductance vessels . An accentuated vasodilatory response to BNP occurs in ET-1-preconstricted arteries. BNP-induced vasodilation in coronary resistance arteries may be partially mediated via nitric oxide and/or prostaglandin release.