Endothelium-dependent pulmonary artery vasorelaxation is dysfunctional in males but not females after acute lung injury


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Abstract

BackgroundMortality after acute respiratory distress syndrome is higher in males than in females. Gender differences in pulmonary vascular reactivity and local inflammatory response may explain this disparity. We hypothesized that endothelium-dependent pulmonary vasorelaxation is impaired in males and that this effect is related to differences in local inflammatory cytokine expression from the pulmonary vasculature.MethodsPulmonary artery (PA) rings (n = 12–16 per group) were isolated from adult male and female Sprague-Dawley rats treated with endotoxin (Salmonella typhimurium lipopolysaccharide, 20 mg/kg IP) or vehicle (0.9% normal saline), and connected to force transducers for measurement of isometric force displacement. Dose-response curves (0.01-10 μmol/L) to the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator sodium nitroprusside were generated. PA rings were also evaluated for inducible nitric oxide synthase, tumor necrosis factor-alpha, and interleukin 1β messenger RNA (mRNA) by reverse transcriptase-polymerase chain reaction.ResultsEndotoxin had no effect on the maximum PA contraction in males (564.4 ± 37.37 mg vs 633.3 ± 54.67 mg vehicle) or females (446.3 ± 20.00 mg vs 444.2 ± 33.02 mg vehicle), but endothelium-dependent vasodilation was significantly decreased in males (47.49 ± 5.63% vs 77.61 ± 9.41% vehicle). Endothelium-independent vasodilation remained intact during endotoxemia. Endotoxin increased the PA expression of inducible nitric oxide synthase mRNA, but there was no gender difference. There was no change in expression of PA tumor necrosis factor, whereas endotoxemic males, but not females, had increased interleukin 1β mRNA, compared with vehicle.ConclusionsThese results suggest that sepsis-induced vascular dysfunction differs between males and females, and, therefore, treatment of acute lung injury may require gender-specific therapies.

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