Altered reactivity of coronary arteries located distal to a chronic coronary occlusion.

The coronary vasculature located distal to a chronic occlusion (collateral-dependent) has been shown to exhibit altered reactivity to vasoactive agonists. Thus we evaluated effects of chronic coronary artery occlusion on vasomotor responsiveness of collateral-dependent arteries isolated from a canine model of Ameroid occlusion of the left circumflex (LCX) coronary artery. We compared in vitro responses of large (∼1.3- to 1.4-mm-ID) and small (∼0.6-mm-ID) LCX arteries located distal to an occlusion with responses of similar-sized segments of the unoccluded left anterior descending (LAD) coronary artery. α-Adrenergic receptor-mediated contractile responses to norepinephrine (10-9-10-4M) and phenylephrine (10-9-10-4M) in the presence of propranolol were markedly enhanced in large LCX arteries compared with LAD arteries ( P< 0.001). Prazosin (1 μM), an α1-adrenergic receptor antagonist, abolished contractile responses of LCX and LAD arteries to norepinephrine. Inhibition of nitric oxide synthesis with N ω-nitro-l-arginine methyl ester (100 μM) enhanced norepinephrine-induced contractions of LAD arteries to a greater extent than contractions of LCX arteries. We simultaneously measured myoplasmic free Ca2+ (fura 2 fluorescence ratio) and contractile responses in LCX and LAD arteries denuded of endothelium; norepinephrine-induced increases in myoplasmic free Ca2+ and contractile tension were significantly enhanced in LCX arteries compared with LAD arteries. In addition, large and small LCX arteries exhibited impaired relaxation in response to adenosine (10-8-10-3M) compared with LAD arteries ( P < 0.05). In contrast, relaxation in response to the β-adrenergic agonist isoproterenol (10-9-10-4M) and sodium nitroprusside (10-10-10-4M) was not significantly different in LCX and LAD arteries. Thus collateral-dependent coronary arteries exhibit enhanced α-adrenergic vasoconstriction and impaired vasorelaxation in response to adenosine. The enhanced α-adrenergic contractile responsiveness involves at least two mechanisms: 1) enhanced α1-adrenergic reactivity of smooth muscle and 2) decreased α-adrenergic-induced synthesis of nitric oxide by the endothelium.