RESPONSE OF COLLATERAL-DEPENDENT MYOCARDIUM TO VASOPRESSIN RELEASE DURING PROLONGED INTENSE EXERCISE

We hypothesized that vasopressin concentrations during exercise attenu ate the increase in collateral-dependent blood flow leading to left ve ntricular dysfunction in Ameroid-occluded miniswine. An Ameroid occlud er was placed around the proximal left circumflex coronary artery (LCX ) of 19 miniswine. Ten weeks later V1 receptor blockade with the use o f [d(CH2)5Tyr(Me)]arginine vasopressin (10-12 mug/kg iv) increased res ting transmural flow (radioactive microspheres) in the LCX region, ind icating the presence of V1 receptors. Neither injection of lysine vaso pressin (125 pmol/kg) after V1 receptor blockade nor injection of two specific V2 receptor agonists caused changes in mean arterial pressure , heart rate, or left anterior descending coronary arterial flow veloc ity, indicating that V2 receptors mediate no appreciable vasodilation in the swine coronary circulation. Next the ratio of collateral to non collateral flow and regional systolic wall thickening (sonomicrometer dimension gauges) were measured at rest and after 20 min of prolonged, intense treadmill exercise (85-90% of heart rate reserve) in the pres ence and absence of V1 receptor antagonism. This degree of exertion in creased plasma lysine vasopressin from 6.2 +/- 1.0 at rest to 21.0 +/- 7.0 pg/ml (P < 0.05) during the unblocked run. However, the decrease in transmural blood flow ratio (collateral to noncollateral flow) from rest was similar during exercise before and after V1 receptor blockad e (0.78 +/- 0.07 and 0.80 +/- 0.05, respectively; P < 0.05 vs. rest). Likewise, percent systolic wall thickening in the collateral-dependent region decreased from rest to exercise in the absence and presence of V1 receptor antagonism (35.9 +/- 4.5 and 39.5 +/- 3.8%, respectively; P < 0.05 vs. rest). Because V1 receptor blockade caused a significant reduction in mean and diastolic pressure during treadmill running, si x pigs performed the same two exercise protocols except that dextran w as infused during the V1 receptor blockade run to match blood pressure s to those obtained during the unblocked run. Similar transmural blood flow ratios and systolic wall thickening responses were still observe d before and after blockade. We conclude that coronary vasodilatory me tabolites released during prolonged, intense exercise predominate over the potential vasoconstrictor effects of vasopressin.