Role of Nitric Oxide Carried by Hemoglobin in Cardiovascular Physiology: Developments on a Three-Gas Respiratory Cycle.

Role of Nitric Oxide Carried by Hemoglobin in Cardiovascular Physiology: Developments on a Three-Gas Respiratory Cycle. Circ Res. 2019 Oct 08;: Authors: Premont RT, Reynolds JD, Zhang R, Stamler JS Abstract A continuous supply of oxygen is essential for the survival of multi-cellular organisms. The understanding of how this supply is regulated in the microvasculature has evolved from viewing erythrocytes (red blood cells, RBCs) as passive carriers of oxygen to recognizing the complex interplay between hemoglobin and oxygen, carbon dioxide, and nitric oxide - the three-gas respiratory cycle - that insures adequate oxygen and nutrient delivery to meet local metabolic demand. In this context, it is blood flow not blood oxygen content that is the main driver of tissue oxygenation by RBCs. Herein we review the lines of experimentation that led to this understanding of RBC function; from the foundational understanding of allosteric regulation of oxygen binding in hemoglobin in the stereochemical model of Perutz, to blood flow autoregulation (hypoxic vasodilation governing oxygen delivery) observed by Guyton, to current understanding that centers on S-nitrosylation of hemoglobin (aka S nitrosohemoglobin; SNO-Hb) as a purveyor of oxygen-dependent vasodilatory activity. Notably, hypoxic vasodilation is recapitulated by native SNO-replete RBCs and by SNO-Hb itself, whereby SNO is released from hemoglobin and RBCs during deoxygenation, in propo...
Source: Circulation Research - Category: Cardiology Authors: Tags: Circ Res Source Type: research