Loss of TRPV4 function causes a deficiency in ventilation/perfusion (V/Q) matching and arterial oxygenation. (A) Control (Trpv4^+/+) or Trpv4^−/− mice were ventilated as described in Materials and Methods section. Normal saline 25 μl was instilled intratracheally, and mice were ventilated for further 2 min. A blood sample was taken from the internal carotid artery for blood gas analysis. Data indicate the p_aO₂ at this point as a percentage of baseline p_aO₂ before saline administration. Note the worsened degree of hypoxemia in Trpv4^−/− mice compared with controls. Data are mean ± SEM for five mice per condition. *P < 0.001 (B) Control (Trpv4^+/+) or Trpv4^−/− mice were anesthetized and endobronchially intubated to selectively ventilate the left lung. After 5 min, a bolus of fluorescent microspheres was delivered to the right atrium via the jugular vein. Mice were sacrificed, and each lung was dissolved in strong alkali. Dissolved tissue was filtered, and fluorescence assessed using a plate reader. Data are presented as the percent difference in perfusion between the ventilated and nonventilated lungs, normalized to lung tissue weight, and demonstrate a failure of pulmonary blood flow redistribution in Trpv4^−/− mice compared with wild-type controls. Data are mean ± SEM for four mice per condition; *P < 0.001.