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NADH: sensor of blood flow need in brain, muscle, and other tissues
Author(s) -
Ido Yasuo,
Chang Katherine,
Woolsey Thomas A.,
Williamson Joseph R.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0652fje
Subject(s) - blood flow , flow sensor , chemistry , cerebral blood flow , biomedical engineering , neuroscience , biophysics , medicine , cardiology , biology , physics , acoustics
The sensor for blood‐flow need with neural activity and exercise is not known. We tested the hypothesis that accumulation of electrons in cytosolic free nicotinamide adenine dinucleotide (NAD) activates redox signaling pathways to augment blood flow. NAD is the primary carrier of electrons from glucose and lactate for ATP synthesis. Because increased glycolysis transfers electrons from glucose to NAD + faster than they are used for mitochondrial ATP synthesis, electrons accumulate in cytosolic NADH. Because cytosolic NADH and intra‐and extracellular lactate/pyruvate (L/P) ratios are all in near‐equilibrium, NADH can be increased or decreased by i.v. lactate or pyruvate. Here, we report that elevated plasma L/P in normal rats increases blood flow in numerous resting tissues and augments blood flow increases in activated somatosensory (barrel) cortex and contracting skeletal muscle. Increased flows are largely prevented by injection of pyruvate (to lower L/P), a superoxide dismutase mimic (to block vascular effects of superoxide), or an inhibitor of nitric oxide synthase (to block NO vasodilation). Electrons carried by NADH, in addition to fueling ATP synthesis, also fuel redox signaling pathways to augment blood flow in resting and working tissues. These novel findings are fundamental to understanding blood‐flow physiology and pathology.