Hemoglobin mediated nitrite activation of soluble guanylyl cyclase.
Nitrite has long been known to be vasoactive when present at large concentrations but it was thought to be inactive under physiological conditions. Surprisingly, we have recently shown that supraphysiological and near physiological concentrations of nitrite cause vasodilation in the human circulation. These effects appeared to result from reduction of nitrite by deoxygenated hemoglobin. Thus, nitrite was proposed to play a role in hypoxic vasodilation. We now discuss these results in the context of nitrite reacting with hemoglobin and effecting vasodilation and present new data modeling the nitric oxide (NO) export from the red blood cell and measurements of soluble guanylate cyclase (sGC) activation. We conclude that NO generated within the interior of the red blood cell is not likely to be effectively exported directly as nitric oxide. Thus, an intermediate species must be formed by the nitrite/deoxyhemoglobin reaction that escapes the red cell and effects vasodilation.
Jeffers
Anne
A
Department of Physics, Wake Forest University, Winston-Salem, NC, 27109-7507 USA.
Xu
Xiuli
X
Huang
Kris T
KT
Cho
Man
M
Hogg
Neil
N
Patel
Rakesh P
RP
Kim-Shapiro
Daniel B
DB
D000818:Animals; D001681:Biological Assay; D002460:Cell Line; D003198:Computer Simulation; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004058:Diffusion; D004789:Enzyme Activation; D004912:Erythrocytes / Q000378:metabolism; D006162:Guanylate Cyclase; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007313:Insecta; D008954:Models, Biological; D008956:Models, Chemical; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism; D009573:Nitrites / Q000737:chemistry*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase; D014664:Vasodilation
D006454:Hemoglobins; D009573:Nitrites; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP