Effects of S-nitrosation of hemoglobin on hypoxic pulmonary vasoconstriction and nitric oxide flux

American Journal of Respiratory and Critical Care Medicine
S DeemE R Swenson

Abstract

Free hemoglobin (Hb) augments hypoxic pulmonary vasoconstriction (HPV), ostensibly by scavenging nitric oxide (NO). However, recent evidence suggests that Hb that is S-nitrosated may act as an NO donor and vasodilator. We studied the effects of oxyHb, Hb that is chemically modified to prevent heme binding or oxidation of NO (cyanometHb), and Hb that is S-nitrosated (SNO-Hb and SNO-cyanometHb) on HPV, expired NO (eNO), and perfusate S-nitrosothiol (SNO) concentration in isolated, perfused rabbit lungs. Perfusate containing either 4 microM oxyHb or SNO-Hb increased normoxic pulmonary artery pressure (Ppa), augmented HPV dramatically, and resulted in an 80% fall in eNO in comparison to perfusion with buffer, whereas 4 microM cyanometHb or SNO-cynanometHb had no effect on these variables. Excess glutathione (GSH) added to perfusate containing SNO-Hb resulted in a 20 to 40% fall in the perfusate SNO concentration, with a concomitant increase in metHb content, without affecting Ppa, HPV, or eNO. In conclusion, free Hb augments HPV by scavenging NO, an effect that is not prevented by S-nitrosation. NO released from SNO-Hb in the presence of GSH does not produce measurable vascular effects in the lung or changes in eNO because of immed...Continue Reading

References

Jan 1, 1990·Methods in Enzymology·C C Winterbourn
Mar 1, 1989·Journal of Applied Physiology·G M MazmanianM Weiss
Apr 1, 1995·Journal of Applied Physiology·F GrimmingerW Seeger
Mar 1, 1995·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·N F VoelkelT J Burke
Nov 1, 1993·Journal of Applied Physiology·J Iwamoto, F C Morin
Nov 5, 1997·Pflügers Archiv : European journal of physiology·L TamayoC González
May 1, 1998·American Journal of Respiratory and Critical Care Medicine·S DeemM J Bishop
May 21, 1999·The Journal of Biological Chemistry·R P PatelV M Darley-Usmar
Jul 20, 1999·Journal of Applied Physiology·S DeemE R Swenson
Aug 24, 1999·The Journal of Biological Chemistry·C BonaventuraR D Stevens
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·S S Gross, P Lane
Oct 8, 1999·The Journal of Clinical Investigation·M T GladwinF P Ognibene
Aug 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·M T GladwinA N Schechter

❮ Previous
Next ❯

Citations

Mar 3, 2004·Free Radical Biology & Medicine·Steven Deem
Sep 19, 2002·Trends in Pharmacological Sciences·Adrian J HobbsAnthony R Butler
Aug 17, 2006·Antioxidants & Redox Signaling·Tara K BurkeAnn L Baldwin
Feb 28, 2007·Clinical and Experimental Pharmacology & Physiology·M HüblerT Koch
Jul 19, 2002·Proceedings of the National Academy of Sciences of the United States of America·Mahesh S JoshiJack R Lancaster
Jul 17, 2004·Free Radical Biology & Medicine·Eric J FrehmAndrew J Gow
Aug 7, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Steven DeemMark T Gladwin
May 2, 2003·Nature Medicine·Mark T GladwinAlan N Schechter
Oct 3, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Steven DeemErik R Swenson
Feb 3, 2012·Physiological Reviews·J T SylvesterJeremy P T Ward
May 23, 2002·The Journal of Biological Chemistry·Mark T GladwinAlan N Schechter

❮ Previous
Next ❯

Related Concepts

Related Feeds

American Thoracic Association Journals

Discover the latest respiratory research published by the journals from the American Thoracic Society.