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Am J Physiol Heart Circ Physiol 273: H1879-H1887, 1997;
0363-6135/97 $5.00
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Vol. 273, Issue 4, H1879-H1887, October 1997

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

Julie A. Rapps, Michael Sturek, Allan W. Jones, and Janet L. Parker

Department of Physiology and Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri 65211

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. alpha -Adrenergic receptor-mediated contractile responses to norepinephrine (10-9-10-4 M) and phenylephrine (10-9-10-4 M) in the presence of propranolol were markedly enhanced in large LCX arteries compared with LAD arteries (P < 0.001). Prazosin (1 µM), an alpha 1-adrenergic receptor antagonist, abolished contractile responses of LCX and LAD arteries to norepinephrine. Inhibition of nitric oxide synthesis with Nomega -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 (10-8-10-3 M) compared with LAD arteries (P < 0.05). In contrast, relaxation in response to the beta -adrenergic agonist isoproterenol (10-9-10-4 M) and sodium nitroprusside (10-10-10-4 M) was not significantly different in LCX and LAD arteries. Thus collateral-dependent coronary arteries exhibit enhanced alpha -adrenergic vasoconstriction and impaired vasorelaxation in response to adenosine. The enhanced alpha -adrenergic contractile responsiveness involves at least two mechanisms: 1) enhanced alpha 1-adrenergic reactivity of smooth muscle and 2) decreased alpha -adrenergic-induced synthesis of nitric oxide by the endothelium.

coronary artery occlusion; norepinephrine; phenylephrine; adenosine; myoplasmic free calcium


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