Endothelin-dependent effects limit flow-induced dilation of conductance coronary vessels after blockade of nitric oxide formation in conscious dogs

Objective: To determine whether endothelin (ET)-dependent effects limit she ar stress-induced dilation of large epicardial coronary arteries after bloc kade of nitric oxide (NO) formation. Methods: In conscious dogs instrumente d for measuring coronary blood flow (CBF) and external diameter (CD) of the circumflex coronary artery, flow-dependent CD dilation was elicited by int racoronary (ic) adenosine (500 ng kg(-1) min(-1)). Results: Ic adenosine in creased CBF by 28+/-4 from 38+/-5 mi min(-1) and CD by 0.25+/-0.03 from 3.5 3+/-0.07 mm without other hemodynamic effects. After N-omega-nitro-L-argini ne methyl ester (L-NAME), baseline CD fell (P<0.01) to 3.35+/-0.08 mm but C BF was not significantly altered (36+/-5 mi min(-1)). CBF increases caused by adenosine were smaller (17+/-2 mi min(-1), P<0.05) and CD responses were nearly abolished (0.02+/-0.01 mm, P<0.01). Ic Ro 61-1790, an ETA receptor blocker, given after L-NAME did not significantly influence baseline CBF (3 6+/-5 mi min(-1)) but increased (P<0.01) CD to 3.45+/-0.09 mm. CBF response s to adenosine were not significantly altered by Ro 61-1790 but CD response s (0.10+/-0.01 mm) were partially restored (P<0.01). In contrast, blockade of ET, receptors with Ro 46-8443 after L-NAME had no further effects on CD and CBF responses to adenosine. Conclusion: ETA receptor-mediated effects l imit flow-dependent dilation of large epicardial coronary arteries in consc ious dogs. Suppression of the L-arginine/NO-dependent pathway with L-NAME r eveals significant ET-dependent effects. (C) 2000 Elsevier Science B.V. All rights reserved.