Due to its relaxant effect in vascular smooth muscle cells, the phosphodiesterase type-V (PDE-V) inhibitor sildenafil has proven beneficial in the treatment of various vascular disorders. Recently, expression of PDE-V has also been identified in endothelial cells. We studied the effects of sildenafil on lung endothelial responses to hydrostatic pressure and resulting changes in capillary filtration coefficient (K_fc ). In isolated perfused rat lungs, we measured endothelial Ca²⁺ concentration ([Ca²⁺]_i) by in situ fura-2 ratio imaging and K_fc by gravimetry at left atrial pressure (P _LA ) of 3 cmH₂O (baseline) and following 20 min P_LA elevation to 8 (for K_fc ) and 15 (for [Ca ²⁺]_i) cmH₂O, respectively. In control lungs, P_LA elevation increased [Ca²⁺]_i from 106±7 nM to 147±5 nM (n=5, p<0.05) and K _fc from 0.4±0.1 to 2.6±0.7 ml•min^-1•cmH₂O1•100 g^-1 (n=5, p<0.05). Sildenafil (0.4 mM) did not affect baseline [Ca²⁺]_i (101±1 nM) and K _fc (0.4±0.1 ml•min^-1•cmH₂O1•100 g^-1) but attenuated the increases of both endothelial Ca²⁺ (110±2 nM; n=5, p<0.05 vs. control) and K _fc (0.9±0.1 ml•min1•cmH₂O^-1•100 g^-1) in response to P_LA elevation (n=5 each, p<0.05). Our data indicate that sildenafil may reduce cardiogenic lung edema. Attenuation of pressure-induced endothelial [Ca²⁺]_i responses may contribute to this protective effect. Sponsored by Pfizer GmbH and Kaiserin-Friedrich Foundation