Prostacyclin analogs and PDE 5 inhibitors synergistically stimulate ATP release from human RBCs

Prostacyclin (PGI2) and phosphodiesterase 5 (PDE5) inhibitors are vasodilators used in the treatment of pulmonary arterial hypertension (PAH). Although these drugs stimulate vascular dilation directly, erythrocytes also express the PGI2 receptor (IPR) and contain PDE5. We determined that PDE5 inhibitors potentiate IPR-mediated release of the potent vasodilator, adenosine triphosphate (ATP) from erythrocytes. These results demonstrate a novel synergism between IPR agonists and PDE5 inhibitors that could provide a new rationale for the treatment of PAH.