Exercise training restores adenosine-induced relaxation in coronary arteries distal to chronic occlusion

We previously reported that canine collateral-dependent coronary arteries e xhibit impaired relaxation to adenosine but not sodium nitroprusside. In co ntrast, exercise training enhances adenosine sensitivity of normal porcine coronary arteries. These results stimulated the hypothesis that chronic cor onary occlusion and exercise training produce differential effects on cAMP- versus cGMP-mediated relaxation. To test this hypothesis, Ameroid occluders were surgically placed around the proximal left circumflex coronary artery (LCx) of female Yucatan miniature swine 8 wk before initiating sedentary o r exercise training (treadmill run, 16 wk) protocols. Relaxation to the cAM P-dependent vasodilators adenosine (10(-7) to 10(-3) M) and isoproterenol ( 3 x 10(-8) to 3 x 10(-5) M) were impaired in collateral-dependent LCx versu s nonoccluded left anterior descending (LAD) arterial rings isolated from s edentary but not exercise-trained pigs. Furthermore, adenosine-mediated red uctions in simultaneous tension and myoplasmic free Ca2+ were impaired in L Cx versus LAD arteries isolated from sedentary but not exercise-trained pig s. In contrast, relaxation in response to the cAMP-dependent vasodilator fo rskolin (10(-9) to 10(-5) M) and the cGMP-dependent vasodilator sodium nitr oprusside (10(-9) to 10(-4) M) was not different in LCx versus LAD arteries of sedentary or exercise-trained animals. These data suggest that chronic occlusion impairs receptor-dependent, cAMP-mediated relaxation; receptor-in dependent cAMP- and cGMP-mediated relaxation were unimpaired. Importantly, exercise training restores cAMP-mediated relaxation of collateral-dependent coronary arteries.