Effects of Ischemia on the Canine Myocardial β-Adrenoceptor-Linked Adenylate Cyclase System

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Abstract
Several studies indicate that myocardial ischemia causes a redistribution of β-adrenergic receptors from a presumably intracellular compartment to the cell surface. However, a decreased adenylate cyclase and contractile responsiveness to β-adrenergic stimuli has also been reported. The aim of the present study was to investigate possible ischemia-induced changes in myocardial β-adrenoceptor coupling to adenylate cyclase. Myocardial ischemia was induced by hydraulic occlusion of the LAD in mongrel dogs anesthetized with isoflurane. After 90 min of ischemia, tissue samples were removed from the ischemic and nonischemic regions for tissue catecholamine determinations and for the preparation of participate fractions from tissue homogenates. Saturation experiments on microsomal fractions obtained from the ischemic and control areas did not reveal any significant changes in the calculated dissociation constant for (–) [125I]- iodocyanopindolol binding nor in the calculated receptor density. Likewise, the relative numbers of β2-adrenergic receptors were comparable in both preparations (–20%). On the other hand, the proportion of β-adrenoceptors stabilized in the high-affinity state by (–)isoproterenol was significantly reduced in the ischemic region when compared with the control myocardium (17 ± 5 vs. 41 ± 4%). This change was accompanied by a significant decrease in the intrinsic activity of (–)isoproterenol in stimulating adenylate cyclase activity. We propose that the initial uncoupling of the β-adrenoceptor from its effector is a physiologically important, protective mechanism which guards the ischemic myocardium against the deleterious effect of excessive sympathetic stimulation.

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