Sildenafil, a potent type 5 nucleotide-dependent phosphodiesterase (PDE) inhibitor, has been recently proposed as a therapeutic tool to treat or prevent pulmonary artery hypertension (PAHT). We thus studied the effect of sildenafil on both the calcium signaling of isolated pulmonary artery smooth muscle cells (PASMCs) and the reactivity of pulmonary artery (PA) obtained from chronic hypoxia (CH)-induced pulmonary hypertensive rats in comparison with control (normoxic) rats. CH rats were maintained in an hypobaric chamber (50.5 kPa) for three weeks leading to full development of PAHT. Intracellular calcium concentration ([Ca²⁺]_i) was measured in PASMCs loaded with the calcium fluorophore indo- 1. Unlike in control rats, sildenafil (10-100 nM) decreased the resting [Ca²⁺]_i value in PASMCs obtained from CH rats. In PASMCs from both control and CH rats, sildenafil concentration-dependently inhibited the [Ca²⁺]_i response induced by G-coupled membrane receptor agonists such as angiotensin II and phenylephrine but had no effect on the amplitude of the [Ca²⁺]_i response induced by caffeine. Sildenafil (0.1 nM - 1 µM) concentrationdependently reduced basal PA tone that is present in CH rats and relaxed PA rings precontracted with phenylephrine both in control and CH rats. These data show that sildenafil is a potent pulmonary artery relaxant in CH rats and that it normalizes CH-induced increases in resting [Ca²⁺]_i and basal tone. Consequently, pharmacological inhibition of sildenafilsensitive PDE5 down regulates the Ca signaling pathway involved in this model of pulmonary hypertension.