Activation of TRPV4 expressed in lung increases endothelial permeability. In human (A), rat (B), and mouse (C) lung, TRPV4 was expressed in the alveolar septal compartment (left panels) and in bronchial epithelium (not shown). TRPV4 expression in vascular smooth muscle in extra-alveolar vessels (right panels) was observed in human and rat lung, whereas little was seen in mouse lung. Western blotting (D) showed similar TRPV4 expression in rat microvascular (MV) and pulmonary artery (PA) endothelium (TRPV4/β-actin band density was 1.1 in both groups). However, TRPV4 was not consistently expressed in endothelium of extra-alveolar vessels in intact lung (A–C). The TRPV4 agonist 4αPDD increased the filtration coefficient Kf in isolated rat lung (p=0.021) in a dose-dependent fashion (p=0.002); *p<0.05 vs 1 or 5 μmol/L. The TRPV1 agonist 4α-phorbol-12,13-didecanoate-20-homovanillate (4αPDDHV) had no effect (p=0.201, paired t-test).