Phosphodiesterase inhibition improves agonist-induced relaxation of hypertensive pulmonary arteries

Pulmonary artery (PA) relaxation in response to vasodilators is significantly attenuated in models of hypoxia-induced pulmo-nary hypertension (HPH). The activity of phosphodiesterases (PDE) which hydrolyze vasodilatory second messengers may be increased by HPH, which thereby contributes to attenuated vasodilatory responses. The purpose of this study was to de-termine the effect of PDE inhibition on agonist-induced relax-ation of PA from normal rats and rats with HPH (FIO2, 0.1 for 14 days). Isolated PA rings were suspended in baths containing Krebs-Henseliet salt solution and contracted with U46619 in the presence or absence of a PDE3 (milrinone) or PDE4 (rolip-ram) inhibitor. Isoproterenol and forskolin induced concentra-tion-dependent relaxation of PA rings from normal rats and rats with HPH, but the degree of relaxation was significantly les