HIGHLIGHTED TOPIC Pulmonary Circulation and Hypoxia NOS3 deficiency augments hypoxic pulmonary vasoconstriction and enhances systemic oxygenation during one-lung ventilation in mice

Liu, Rong, Oleg V. Evgenov, and Fumito Ichinose. NOS3 deficiency augments hypoxic pulmonary vasoconstriction and enhances systemic oxygenation during one-lung ventilation in mice. J Appl Physiol 98: 748–752, 2005. First published October 1, 2004; doi:10.1152/japplphysiol.00820.2004.—Nitric oxide (NO), synthesized by NO synthases (NOS), plays a pivotal role in regulation of pulmonary vascular tone. To examine the role of endothelial NOS (NOS3) in hypoxic pulmonary vasoconstriction (HPV), we measured left lung pulmonary vascular resistance (LPVR), intrapulmonary shunting, and arterial PO2 (PaO2) before and during left mainstem bronchus occlusion (LMBO) in mice with and without a deletion of the gene encoding NOS3. The increase of LPVR induced by LMBO was greater in NOS3-deficient mice than in wild-type mice (151 39% vs. 109 36%, mean SD; P 0.05). NOS3-deficient mice had a lower intrapulmonary shunt fraction than wild-type mice (17.1 3.6% vs. 21.7 2.4%, P 0.05) during LMBO. Both real-time PaO2 monitoring with an intra-arterial probe and arterial blood-gas analysis during LMBO showed higher PaO2 in NOS3deficient mice than in wild-type mice (P 0.05). Inhibition of all three NOS isoforms with N -nitro-L-arginine methyl ester (L-NAME) augmented the increase of LPVR induced by LMBO in wild-type mice (183 67% in L-NAME treated vs. 109 36% in saline treated, P 0.01) but not in NOS3-deficient mice. Similarly, systemic oxygenation during one-lung ventilation was augmented by L-NAME in wild-type mice but not in NOS3-deficient mice. These findings indicate that NO derived from NOS3 modulates HPV in vivo and that inhibition of NOS3 improves systemic oxygenation during acute unilateral lung hypoxia.