Faculty Collaboration Database

Transduction of NO-bioactivity by the red blood cell in sepsis: novel mechanisms of vasodilation during acute inflammatory disease. Blood 2004 Sep 01;104(5):1375-82

Date

05/20/2004

Pubmed ID

15150083

DOI

10.1182/blood-2004-03-0880

Scopus ID

2-s2.0-4444248457 (requires institutional sign-in at Scopus site)   104 Citations

Abstract

Sepsis is an acute inflammatory disease characterized by dysfunctional blood flow and hypotension. Nitric oxide (NO) is elevated during sepsis and plays an integral role in the associated vascular pathology. However, precise mechanisms and functions of NO in sepsis remain unclear. In this study, we show that red blood cells (RBCs) are foci for nitrosative reactions during acute inflammation, resulting in the formation of cells that can promote systemic vascular relaxation in an uncontrolled manner. Specifically, using experimental models of endotoxemia and surgical sepsis, NO adducts were found in the RBCs, including S-nitrosohemoglobin (SNOHb). These RBCs, referred to as septic RBCs, spontaneously stimulated vasodilation in a manner consistent with elevated SNOHb concentrations. Moreover, relaxation was cyclic guanosine monophosphate (cGMP) dependent and was inhibited by RBC lysis and glutathione but not by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline 1-oxyl 3-oxide (C-PTIO). The potential mechanism of septic RBC-mediated vasorelaxation is discussed and may involve the intermediate, nitroxyl (HNO). Coupled with data showing that NO adducts in septic RBCs were dependent on the inducible nitric oxide synthase and correlated with plasma nitrite, these findings provide a novel framework to understand mechanisms underlying dysfunctional blood flow responses during sepsis. Specifically, the concept that RBCs directly mediate systemic hypotension through NO-dependent mechanisms is discussed.

Author List

Crawford JH, Chacko BK, Pruitt HM, Piknova B, Hogg N, Patel RP

Author

Neil Hogg PhD Senior Associate Dean, Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Disease
Animals
Cecum
Disease Models, Animal
Erythrocytes
Hemoglobins
Ligation
Lipopolysaccharides
Male
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nitrites
Oxygen
Rats
Rats, Sprague-Dawley
Sepsis
Vasodilation
Wounds, Stab