The NO donor sodium nitroprusside: evaluation of skeletal muscle vascular and metabolic dysfunction

Abstract

The nitric oxide (NO) donor sodium nitroprusside (SNP) may promote cyanide-induced toxicity and systemic and/or local responses approaching maximal vasodilation. The hypotheses were tested that SNP superfusion of the rat spinotrapezius muscle exerts 1) residual impairments in resting and contracting blood flow, oxygen utilization (VO[subscript 2]) and microvascular O[subscript 2] pressure (PO[subscript 2mv]); and 2) marked hypotension and elevation in resting PO[subscript 2mv]. Two superfusion protocols were performed: 1) Krebs-Henseleit (control 1), SNP (300 μM; a dose used commonly in superfusion studies) and Krebs-Henseleit (control 2), in this order; 2) 300 and 1200 μM SNP in random order. Spinotrapezius muscle blood flow (radiolabeled microspheres), VO[subscript 2] (Fick calculation) and PO[subscript 2mv] (phosphorescence quenching) were determined at rest and during electrically-induced (1 Hz) contractions. There were no differences in spinotrapezius blood flow, VO[subscript 2] or PO[subscript 2mv] at rest and during contractions pre- and post-SNP condition (control 1 and control 2; p>0.05 for all). With regard to dosing, SNP produced a graded elevation in resting PO[subscript 2mv] (p<0.05) with a reduction in mean arterial pressure only at the higher concentration (p<0.05). Contrary to our hypothesis, skeletal muscle superfusion with the NO donor SNP (300 μM) improved microvascular oxygenation during the transition from rest to contractions (PO[subscript 2mv] kinetics) without precipitating residual impairment of muscle hemodynamic or metabolic control or compromising systemic hemodynamics. These data suggest that SNP superfusion (300 μM) constitutes a valid and important tool for assessing the functional roles of NO in resting and contracting skeletal muscle function without incurring residual alterations consistent with cyanide accumulation and poisoning.