Sex differences in skin microcirculatory vascular reactivity in experimental lipopolysaccharide-induced endotoxinemia

Abstract

Bacterial lipopolysaccharide (LPS) plays a leading role in the development of a systemic inflammatory response and endogenous intoxication. However, the sex differences in the functional state of the microcirculatory bed in LPS-induced endotoxinemia have been poorly studied. Objective. To study the characteristics of skin microcirculatory vascular reactivity in experimental LPS-induced endotoxinemia in male and female rats. Material and methods. Modeling of endotoxinemia was performed by intraperitoneal injection of LPS of the cell wall of the bacterium Salmonella enterica to male and female Wistar stock rats. Two doses of LPS were used: 50 mg/kg and 10 mg/kg. We used laser Doppler flowmetry to evaluate skin perfusion before and after LPS injection, blood flow changes under test conditions with local contact hypothermia caused by a thermoelement. Results. 48 hours after LPS injection, a decrease in blood flow was observed, especially pronounced at a dose of LPS 50 mg/kg. During the test with local cooling of the skin, a change in the kinetics of the reaction was noted. Blood flow reduction was 75% (LPS 50 mg/kg) and 51% (LPS 10 mg/kg), statistically significantly different from the control groups. At the same time, the classic phenomenon of “cold vasodilation” observed in control rats was absent in all groups with the injection of LPS. Maximum perfusion after restoration of blood flow in females was achieved 3 times faster than in males (LPS 10 mg/kg). Conclusion. In experimental LPS-induced endotoxinemia, a dose-dependent decrease in skin perfusion was revealed. We obtained new data on the absence of pronounced “cold vasodilation” at local contact hypothermia. The results of the study indicate a violation of the mechanisms of neurogenic vasoconstriction and endothelium-dependent vasodilation, reflecting systemic disorders of microcirculation regulation. At the same time, the females showed a more positive dynamics of blood flow restoration in the test with local cooling of the skin, indicating a greater functional reserve and a more effective mechanism of autoregulation of the blood microcirculation system. A functional test with local contact cooling of the skin is highly informative for assessing vascular reactivity and preservation of the autoregulation mechanism of microcirculation in modeling endogenous intoxication