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(Circulation Research. 2004;94:559.)
© 2004 American Heart Association, Inc.

Integrative Physiology

Enhanced S-Nitroso-Albumin Formation From Inhaled NO During Ischemia/Reperfusion

Ella S.M. Ng, David Jourd’heuil, Joe M. McCord, Daniel Hernandez, Mitsukuni Yasui, Derrice Knight, Paul Kubes

From the Department of Physiology and Biophysics (E.S.M.N., D.K., P.K.), Immunology Research Group, University of Calgary, Calgary, Alberta, Canada; Center for Cardiovascular Sciences (D.J.), Albany Medical College, Albany, NY; and Webb-Waring Institute (J.M.M., D.H., M.Y.), University of Colorado Health Sciences Center, Denver, Colo.

Correspondence to Dr Paul Kubes, Immunology Research Group, University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta, Canada, T2N 4N1. E-mail pkubes{at}ucalgary.ca

In the present study, we investigated whether inhaled nitric oxide (NO) was transported by plasma proteins, such as S-nitroso-albumin (SNO-Alb), in the feline circulation and whether this molecule delivers NO to the periphery under conditions of stress, specifically ischemia/reperfusion (I/R). A flow probe was interposed between the femoral and superior mesenteric artery for blood flow measurements, and a branch of the superior mesenteric vein was cannulated for arterial-venous sampling. In animals breathing room air, SNO-Alb was below detection level in arterial or venous blood. NO inhalation resulted in a significant arterial-venous gradient for SNO-Alb. Concomitant with this loss of SNO-Alb across the intestinal vasculature was an increase in nitrite (NO₂^-). However, this release of NO was not sufficient to alter intestinal blood flow. I/R during NO inhalation caused a very large increase in arterial SNO-Alb that permitted a 5-fold increase in SNO-Alb consumption and significant generation of NO₂^- within the postischemic intestinal vasculature. The increased SNO-Alb consumption was sufficient to dramatically improve intestinal blood flow. The very large burst of arterial SNO-Alb during I/R was completely blocked by the administration of superoxide dismutase, suggesting that oxidative stress contributed to the increased SNO-Alb formation. Our data suggest that inhaled NO can increase nitrosothiol production and these molecules may be a functional NO delivery system during cardiovascular disease.

Key Words: S-nitroso-albumin • oxidative stress • postischemic vasculature

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