#WHY DOES VOLUMETRIX FLOW DECREASE AS REACTION PROCEEDS SERIES#
The enzymatic formation of NO is catalyzed by nitric oxide synthase (NOS) through a series of redox reactions. A recent review assessed the role of NO regulation of microvascular oxygenation ( 12).Įndogenous NO is derived from both enzymatic and nonenzymatic sources in and near the vasculature ( Fig. Abnormalities in NO production and transport in vascular systems lead to numerous cardiovascular diseases, including hypertension, atherosclerosis, and angiogenesis-associated disorders ( 68, 73, 74). NO affects two key aspects of O 2 supply and demand: It regulates vascular tone and blood flow by activating soluble guanylate cyclase (sGC) in the vascular smooth muscle, and it controls mitochondrial O 2 consumption by inhibiting cytochrome c oxidase. T he past decade has seen a wealth of research regarding nitric oxide (NO), a pivotal signaling molecule that regulates blood flow and tissue oxygenation. Resolving these issues is highly relevant to improving our understanding of vascular biology and to developing pharmaceutical agents that target NO pathways, such as vasodilating drugs. In this study, we review the NO literature, analyzing NO levels on various scales, identifying and analyzing the discrepancies in the reported data, and proposing hypotheses that can potentially reconcile these discrepancies. Large apparent discrepancies exist among the published reports that have analyzed the various pathways in terms of the perivascular NO concentration, the efficacy of NO in causing vasodilation (EC 50), its efficacy in tissue respiration (IC 50), and the paracrine and endocrine NO release. However, significant gaps exist in our quantitative understanding of the regulation of NO production in the vascular region. Nitric oxide (NO) affects two key aspects of O 2 supply and demand: It regulates vascular tone and blood flow by activating soluble guanylate cyclase (sGC) in the vascular smooth muscle, and it controls mitochondrial O 2 consumption by inhibiting cytochrome c oxidase.