Enhanced S-nitroso-albumin formation from inhaled NO during ischemia/reperfusion.
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.
Ng
Ella S M
ES
Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada.
Jourd'heuil
David
D
McCord
Joe M
JM
Hernandez
Daniel
D
Yasui
Mitsukuni
M
Knight
Derrice
D
Kubes
Paul
P
D000280:Administration, Inhalation; D000818:Animals; D001692:Biological Transport; D002415:Cats; D003250:Constriction; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000378:metabolism*; D017538:Mesenteric Artery, Superior; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009573:Nitrites / Q000097:blood; D009603:Nitroso Compounds; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015424:Reperfusion; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000096:biosynthesis*; D013152:Splanchnic Circulation / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000097:blood; D014664:Vasodilation
D020030:Nitric Oxide Donors; D009573:Nitrites; D009603:Nitroso Compounds; D011993:Recombinant Fusion Proteins; C091665:S-nitrosoalbumin; D013481:Superoxides; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester