Effect of phosphodiesterase 5 inhibition on systemic hemodynamics and regional blood flows in exercising swine

Abstract

Phosphodiesterase 5 (PDE5) inhibitors have garnered wide therapeutic use; however, the effect of PDE5 inhibition on blood flow to skeletal muscle, which expresses PDE5, during exercise in healthy animals has not been determined. We therefore investigated the effect of PDE5 inhibition on exercise‐induced vasodilation in vivo with regional blood flows determined using microsphere infusion at rest and during acute exercise. Chronically instrumented swine (n=5) were exercised on a treadmill (0‐5 mph) and systemic hemodynamics and regional blood flows were compared before and during infusion of the PDE5 inhibitor EMD360527 (0.3 mg/kg/min iv). At rest, inhibition of PDE5 had no effect on mean aortic pressure whereas heart rate and cardiac output increased and systemic vascular resistance (SVR) decreased by 17% consistent with peripheral vasodilation. Visceral, cardiac, cerebral and skeletal muscle blood flows were unchanged. The PDE5‐induced reduction in SVR was maintained during acute exercise at 4 mph and blood flows to the superficial portions of the triceps brachii long head and vastus lateralis in the forelimb and hindlimb, respectively, were increased. All other regional blood flows were unchanged. Thus, inhibition of PDE5 induces peripheral vasodilation and preferentially increases skeletal muscle blood flow during acute exercise in swine. Supported by NIH and the Dutch Heart Foundation.