Journal of applied physiology
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Comparative Study
NOS3 deficiency augments hypoxic pulmonary vasoconstriction and enhances systemic oxygenation during one-lung ventilation in mice.
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). ⋯ Inhibition of all three NOS isoforms with Nomega-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.
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Comparative Study
Activation of the vasoactive intestinal peptide 2 receptor modulates normal and atrophying skeletal muscle mass and force.
Of the two known vasoactive intestinal peptide receptors (VPAC1R and VPAC2R), the VPAC2R is expressed in skeletal muscle. To evaluate the function of the VPAC2R in the physiological control of skeletal muscle mass, we utilized the VPAC1R selective agonist [K15,R16,L27]VIP(1-7) GRF(8-27)-NH2 and the VPAC2R selective agonist Ro-25-1553 to treat mice and rats undergoing either nerve damage-, corticosteroid-, or disuse-induced skeletal muscle atrophy. These analyses demonstrated that activation of VPAC2R, but not VPAC1R, reduced the loss of skeletal muscle mass and force during conditions of skeletal muscle atrophy resulting from corticosteroid administration, denervation, casting-induced disuse, increased skeletal muscle mass, and force of nonatrophying muscles. These studies indicate that VPAC2R agonists may have utility for the treatment of skeletal muscle-wasting diseases.
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Comparative Study
Resuscitation with lactated Ringer solution limits the expression of molecular events associated with lung injury after hemorrhage.
The aim of this study was to determine whether hemorrhage altered the caspase-3 activity and the ATP levels in rat lung and ileum tissues and determine whether resuscitation with lactated Ringer solution (LR) or whole blood (WB) reversed these changes. Male Sprague-Dawley rats were briefly anesthetized with isoflurane, and their mean arterial blood pressure was reduced from 110 to 40 mmHg by bleeding. The bled rat was then resuscitated with LR or autologous WB to bring mean arterial blood pressure back to 80 mmHg. ⋯ Similarly, hemorrhage increased the expression of inducible nitric oxide synthase and Kruppel-like factor 6 and decreased expression of Kruppel-like factor 4. Subsequent LR resuscitation normalized the expression of these genes in the lung tissue. Our results demonstrate that resuscitation with LR can reverse the expression of genes and their products that are thought to contribute to hemorrhage-induced lung injury.