Acetylcholine-Induced and Nitric Oxide-Mediated Vasodilation in Burns

Abstract

Microvascular endothelial cells actively participate in local regulation of blood flow and blood–tissue exchange by producing various vasoactive substances including nitric oxide (NO). This study examined microcirculatory changes in the early stage of thermal injury and the NO-related mechanisms. Resistance arterioles of rat cremaster muscle were observed using intravital microscopy. Arteriolar diameter and flow velocity were measured and flow rate was calculated after administration of various vasoactive agonists in burns. In fluid-resuscitated rats with stable systemic blood pressure, microvascular caliber and blood flow were not significantly altered in the first hour following a 25% total body surface area full-thickness scald burn. Topical application of acetylcholine (ACh), an endothelium-dependent vasodilator, increased arteriolar diameter and flow rate in a dose-dependent fashion. The dose–responsive effects of ACh were significantly greater in burned rats than in sham-burned rats, and the augmentation was blocked by inhibition of NO production withNG-monomethyl-l-arginine (L-NMMA). Topical application of adenosine, an endothelium-independent vasodilator, and sodium nitroprusside, an exogenous NO donor, markedly increased arteriolar diameter and flow rate. The effects were not significantly different in burned and sham-burned animals, and the adenosine-induced vasodilation was not blocked by L-NMMA. These data suggest that endothelium-dependent and NO-mediated arteriolar dilation is enhanced in the early stage of thermal injury. This effect may play an important role in the pathophysiological events of microcirculation and blood–tissue exchange in burns.