Ischemic Preconditioning Is Associated With a Delay in Ischemia-Induced Reduction of β-Adrenergic Signal Transduction in Rabbit Hearts

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Abstract

Background.

It has been reported that the A1-adenosine receptor mediates the cardioprotective effect of ischemic preconditioning. This receptor couples inhibitory guanine nucleotide-binding protein (Gi) and inhibits adenylate cyclase activity. However, the role of adenylate cyclase in preconditioning is unknown.

Methods and Results.

We compared the effects of ischemia on the sarcolemmal β-adrenergic receptor density (Bmax), the stimulatory guanine nucleotide-binding protein (Gs) activity as determined by reconstitution with S49 lymphomacyc− membranes, and baseline and maximally stimulated adenylate cyclase activities (ACAs) in control and preconditioned rabbit hearts. The control population (n=28) received 0, 10, 20, and 60 minutes of coronary occlusion (n=6 to 8 per stage), and preconditioned rabbits (n=24) received two cycles of alternating 5-minute occlusion and reperfusion before sustained ischemia (n=6 per stage). In control hearts, occlusion induced rapid and progressive reductions in the Bmax, Gs, and ACAs after 10 to 60 minutes of ischemia. Preconditioning did not affect the reduction in Bmax, but it preserved reductions in Gs activity and ACAs after 10 to 20 but not 60 minutes of sustained ischemia. In another study, 18 rabbits were treated with pertussis toxin 48 hours before surgery to block Gi. During treatment, no significant difference was observed in the ischemia-induced reduction in ACAs in the ischemic region between control (n=8) and preconditioned (n=10) animals after 20 minutes of ischemia.

Conclusions.

Preconditioning delays ischemia-induced reductions in β-adrenergic signal transduction. Inhibition of ACA is not the target effect of the A1-adenosine receptor-Gi pathway responsible for the cardioprotective role of preconditioning. (Circulation.1993;88:2827–2837.)

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