This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kim-Shapiro, D. B. Articles by Hogg, N. Search for Related Content PubMed PubMed Citation Articles by Kim-Shapiro, D. B. Articles by Hogg, N.

(Circulation Research. 2004;95:e10.)
© 2004 American Heart Association, Inc.

Letter to the Editor

How do Red Blood Cells Dilate Blood Vessels?—Reply

Daniel B. Kim-Shapiro

Department of Physics, Wake Forest University, Winston-Salem, NC, shapiro@wfu.edu

Rakesh P. Patel

Department of Pathology, University of Alabama, Birmingham, Ala

Alan N. Schechter

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md

Mark T. Gladwin, Richard O. Cannon, III

National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Md, mgladwin@nih.gov

Neil Hogg

Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wis

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

A recent Letter to the Editor in Circulation Research from Drs. Allen and Piantadosi criticizes some of our recent work and its interpretation.¹ We find that the letter contains significant errors in evaluating our work that we would like to address with the hope that we can resolve some of the issues raised.

Allen and Piantadosi claim that a recent editorial by Gladwin and Schechter,² outlining mechanisms that explain how nitric oxide (NO) is delivered by red blood cells (RBCs), creates a false dichotomy that impedes scientific advance. However, we find that these mechanisms involve fundamentally different biochemical reactivities and differ in both the source of NO and the nature of the oxygen sensing reaction. The first mechanism, proposed by Stamler’s group, suggests that hemoglobin binds NO at the cysteine 93 to form S-nitroso hemoglobin (SNO-Hb), which serves as a storage pool for a circulating S-nitrosothiol; the S-nitrosothiol is released from hemoglobin after a change in hemoglobin quaternary structure from the R (oxygenated) to T (deoxygenated) state. The second mechanism, proposed by our group, suggests that the anion nitrite serves as the storage pool and is converted to NO through heme-based reduction by deoxyhemoglobin.³ The SNO-Hb hypothesis does not invoke nitrite nor heme-based nitrite reduction, and the nitrite reductase hypothesis does not require SNO-Hb as an intermediate. In the interest of real "scientific advancement,"¹ we believe that a complete understanding of the nitrite model will require characterization of the nitrite heme reaction, including coordination . . . [Full Text of this Article]