Hypoxic modulation of exogenous nitrite-induced vasodilation in humans.

HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation

Local vasodilation in response to hypoxia is a fundamental physiologic response ensuring oxygen delivery to tissues under metabolic stress. Recent studies identify a role for the red blood cell (RBC), with hemoglobin the hypoxic sensor. Herein, we investigate the mechanisms regulating this process and explore the relative roles of adenosine triphosphate, S-nitrosohemoglobin, and nitrite as effe...

Nitrite Regulates Hypoxic Vasodilation via Myoglobin–Dependent Nitric Oxide Generation Running title: Totzeck et al.; Nitrite Regulates Hypoxic Vasodilation

Nitrite regulates hypoxic vasodilation via myoglobin-dependent nitric oxide generation.

BACKGROUND Hypoxic vasodilation is a physiological response to low oxygen tension that increases blood supply to match metabolic demands. Although this response has been characterized for >100 years, the underlying hypoxic sensing and effector signaling mechanisms remain uncertain. We have shown that deoxygenated myoglobin in the heart can reduce nitrite to nitric oxide (NO·) and thereby contri...

Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection, and vasodilation.

Accumulating evidence suggests that the simple and ubiquitous anion salt, nitrite (NO(2)(-)), is a physiological signaling molecule with potential roles in intravascular endocrine nitric oxide (NO) transport, hypoxic vasodilation, signaling, and cytoprotection after ischemia-reperfusion. Human and animal studies of nitrite treatment and NO gas inhalation provide evidence that nitrite mediates m...

Nitrite-Mediated Hypoxic Vasodilation Predicted from Mathematical Modeling and Quantified from in Vivo Studies in Rat Mesentery

Nitric oxide (NO) generated from nitrite through nitrite reductase activity in red blood cells has been proposed to play a major role in hypoxic vasodilation. However, we have previously predicted from mathematical modeling that much more NO can be derived from tissue nitrite reductase activity than from red blood cell nitrite reductase activity. Evidence in the literature suggests that tissue ...