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(Circulation Research. 2004;94:414.)
© 2004 American Heart Association, Inc.

Editorials

S-Nitrosothiols in the Blood

Roles, Amounts, and Methods of Analysis

Jonathan S. Stamler

From the Howard Hughes Medical Institute and the Department of Medicine, Duke University Medical Center, Durham, NC.

Correspondence to Jonathan S. Stamler, MD, Department of Medicine, Box 2612, Duke University Medical Center, Durham, NC 27710. E-mail STAML001@mc.duke.edu

Key Words: S-nitrosothiols • nitric oxide • vasodilation

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

In 1991 to 1992, we reported that both endogenous and exogenous nitric oxide (NO) react with thiols in proteins such as albumin to form long-lived S-nitrosothiols (SNOs) with vasodilatory activity.¹ We also described the presence of a circulating pool of S-nitrosoalbumin in plasma whose levels were coupled to NO synthase (NOS) activity. Inhibition of NOS led to a decline in SNO-albumin with concomitant production of low-mass SNOs.² We proposed that SNO-albumin provides a reservoir of NO bioactivity that might be utilized in states of NO deficiency, and that vasodilation by SNO-albumin is transduced by the small-mass SNOs with which it exists in equilibrium. Shortly thereafter,³ we determined that a key low-mass SNO in biological systems is S-nitrosoglutathione (GSNO); that GSNO, in contrast to NO, retained smooth muscle relaxant activity in the presence of blood hemoglobin; and that GSNO is a more potent relaxant than SNO-proteins. Subsequently, we demonstrated the existence of intraerythrocytic equilibria between NO bound to the thiol of glutathione and reactive thiols (cysß93) of hemoglobin on the one hand,⁴ and NO bound to thiols of hemoglobin and membrane-associated band 3 protein (AE1), on the other hand.⁵ The exchange of NO groups between S-nitrosohemoglobin (SNO-Hb) and the red blood cell (RBC) membrane is governed by O₂ tension (PO₂): RBCs dilate blood vessels at low PO₂,^5–7 and the production of membrane SNO is required for vasodilation. In peripheral tissues, blood flow is determined by variations in hemoglobin O₂ saturation that are coupled . . . [Full Text of this Article]

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