Initial data by West and colleagues17 on permeability modification in HF, along with more recent data on transient receptor potential vanilloid (TRPV4) channels that implicated mechanosensitive pressure‐induced changes in the endothelium, led us to hypothesize that higher pulmonary pressures would change tissue permeability, amplify the shift in water to the lung tissue space, and thereby offer another target for HF therapeutics via a novel approach with TRPV4 antagonism. The gene discussed is TRPV4; the disease is hydrops fetalis.