Coronary Blood Flow Responses are Impaired Independent of NO and Endothelial Function in Conscious Dogs with Dilated Cardiomyopathy

Abstract

Background Dilated cardiomyopathy (DCM) is characterized by nitric oxide (NO) deficiency and endothelial dysfunction. Whether endothelium-independent vasodilation is preserved, particularly in the coronary circulation, remains controversial. Methods and Results We studied systemic and coronary flow responses to the endothelium-dependent agonist, acetylcholine, the cGMP-dependent NO-donor, nitroglycerin, the predominantly endothelium-independent agonist, adenosine, the β-adrenergic cAMP-dependent agonist, isoproterenol, and the calcium channel antagonist, nicardipine, in conscious dogs with pacing-induced DCM. Systemic blood flow response was impaired to acetylcholine but preserved to other vasodilators in DCM. In contrast, coronary blood flow response was significantly ( P < .05) depressed to all agonists. (Peak coronary blood flow response, control versus DCM: acetylcholine: 221 ± 14% versus 156 ± 11%; nitroglycerin: 220 ± 17% versus 138 ± 9%; adenosine: 635 ± 65% versus 376 ± 56%; nicardipine: 338 ± 59% versus 115 ± 23%; isoproterenol: 219 ± 18% versus 86 ± 20%). The attenuation was independent of systemic hemodynamic differences. Conclusion In contrast to systemic responses, coronary blood flow responses in DCM are impaired dependent or independent of NO or second messenger mechanisms, implying either distal signaling defects or structural abnormalities in the coronary vasculature.