Hemorrhagic shock resuscitation affects early and selective mesenteric artery endothelial function through a free radical-dependent mechanism

Mesenteric ischemia/reperfusion occurring during hemorrhagic shock and resuscitation (H/R) induces a systemic inflammatory response and damages endothelial cells. Our aim was to investigate whether H/R affects selectively mesenteric vascular reactivity and the roles of free radicals and inducible nitric oxide (NO) synthase (iNOS) in these changes, Rats subjected to H (30 min)/R (60 min) in the presence or absence of the free radical scavenger N-2 mercaptopropionyl glycine (MPG), or the specific inhibitor of iNOS [(3) N-(3-aminomethyl)benzyl) acetaminide; 1400W] were studied. Saline requirements to maintain systemic blood pressure during R (53.4 +/- 5.2 mL/kg/h) were reduced by MPG (26.2 +/- 3.1) and 1400W (37.5 +/- 4.1). H/R reduced maximal mesenteric arteries relaxation to acetylcholine (sham: 70% +/- 5%, H/R: 21% +/- 3%) and this impairment was prevented by MPG (66% +/- 10%) and reduced by 1400W (49% +/- 9%). H/R did not affect the endothelium-independent relaxations. Maximal responses to phenylephrine were reduced in mesenteric arteries by H/R (3.6 +/- 0.5 mN/mm vs. sham 6.5 +/- 0.5), this impairment was prevented by 1400W and MPG. No impaired response to acetylcholine was detected in skeletal muscle arteries. H/R was associated with an increased production of TNF-alpha (169 +/- 8.5 ng/mL vs. sham 38 +/- 5 ng/mL), and this was reduced to 75 8 ng/mL in MPG-treated rats. Total intestinal content of iNOS mRNA was also increased by H/R and this increase was partly reduced by treatment with MPG. H/R induces an early and selective mesenteric endothelial cell dysfunction through a mechanism that involves oxygen-derived free radicals and NO produced by iNOS. H/R is associated with a mesenteric hyporeactivity through an induction of NOS and may be prevented by scavenging free radicals. This early impairment in enclothelial function is associated with a local inflammatory response.