Response of collateral-dependent myocardium to vasopressin release during prolonged intense exercise

We hypothesized that vasopressin concentrations during exercise attenuate the increase in collateral-dependent blood flow leading to left ventricular dysfunction in Ameroid-occluded miniswine. An Ameroid occluder was placed around the proximal left circumflex coronary artery (LCX) of 19 miniswine. Ten weeks later V₁ receptor blockade with the use of [d(CH₂)₅ Tyr- (Me)]arginine vasopressin (10-12 μg/kg iv) increased resting transmural flow (radioactive microspheres) in the LCX region, indicating the presence of V₁ receptors. Neither injection of lysine vasopressin (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 velocity, indicating that V₂ receptors mediate no appreciable vasodilation in the swine coronary circulation. Next the ratio of collateral to noncollateral 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 presence and absence of V₁ receptor antagonism. This degree of exertion increased 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 blockade (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, six pigs performed the same two exercise protocols except that dextran was infused during the V₁ receptor blockade run to match blood pressures to those obtained during the unblocked run. Similar transmural blood flow ratios and systolic wall thickening responses were still observed before and after blockade. We conclude that coronary vasodilatory metabolites released during prolonged, intense exercise predominate over the potential vasoconstrictor effects of vasopressin.