title: Effect of sodium nitrite on local control of contracting skeletal muscle microvascular oxygen pressure in healthy rats.
abstract: Exercise intolerance characteristic of diseases such as chronic heart failure (CHF) and diabetes is associated with reduced nitric oxide (NO) bioavailability from nitric oxide synthase (NOS), resulting in an impaired microvascular O2driving pressure (Po2mv; O2delivery/O2utilization) and metabolic control. Infusions of the potent NO donor sodium nitroprusside augment NO bioavailability yet decrease mean arterial pressure (MAP) thereby reducing its potential efficacy for patient populations. To eliminate or reduce hypotensive sequelae, [Formula: see text] was superfused onto the spinotrapezius muscle. It was hypothesized that local [Formula: see text] administration would elevate resting Po2mv and slow Po2mv kinetics [increased time constant (τ) and mean response time (MRT)] following the onset of muscle contractions without decreasing MAP. In 12 anesthetized male Sprague-Dawley rats, Po2mv of the circulation-intact spinotrapezius muscle was measured by phosphorescence quenching during 180 s of electrically induced twitch contractions (1 Hz) before and after superfusion of sodium nitrite (NaNO230 mM). [Formula: see text] superfusion elevated resting Po2mv (control: 28.4 ± 1.1 vs. [Formula: see text]: 31.6 ± 1.2 mmHg; P ≤ 0.05), τ (control: 12.3 ± 1.2 vs. [Formula: see text]: 19.7 ± 2.2 s; P ≤ 0.05), and MRT (control: 19.3 ± 1.9 vs. [Formula: see text]: 25.6 ± 3.3 s; P ≤ 0.05). Importantly, these effects occurred in the absence of any reduction in MAP (103 ± 4 vs. 105 ± 4 mmHg, pre- and postsuperfusion respectively; P > 0.05). These results indicate that [Formula: see text] supplementation delivered to the muscle directly through [Formula: see text] superfusion enhances the blood-myocyte oxygen driving pressure without compromising MAP at rest and following the onset of muscle contraction. This strategy has substantial clinical utility for a range of ischemic conditions.
  
  
  
  Ischemic conditions as diverse as chronic heart failure (CHF) and frostbite inflict tissue damage via inadequate O2delivery. Herein we demonstrate that direct application of sodium nitrite enhances the O2supply-O2demand relationship, raising microvascular O2pressure in healthy skeletal muscle. This therapeutic action of nitrite-derived nitric oxide occurred without inducing systemic hypotension and has the potential to relieve focal ischemia and preserve tissue vitality by enhancing O2delivery.
authors: Department of Kinesiology, Kansas State University, Manhattan, Kansas; and.
authors: Trenton D
authors: TD
authors: Colburn
authors: Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas.
authors: Scott K
authors: SK
authors: Ferguson
authors: Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas.
authors: Clark T
authors: CT
authors: Holdsworth
authors: Department of Kinesiology, Kansas State University, Manhattan, Kansas; and.
authors: Jesse C
authors: JC
authors: Craig
authors: Department of Kinesiology, Kansas State University, Manhattan, Kansas; and.|Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas.
authors: Timothy I
authors: TI
authors: Musch
authors: Department of Kinesiology, Kansas State University, Manhattan, Kansas; and poole@vet.ksu.edu.|Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas.
authors: David C
authors: DC
authors: Poole
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism; D007022:Hypotension / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D032342:Muscle Cells / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012977:Sodium Nitrite / Q000494:pharmacology*
chemical_list: D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D012977:Sodium Nitrite; D010100:Oxygen
keywords: beetroot; blood flow; exercise; microcirculation; nitrate; nitric oxide; oxygen delivery; vascular control