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• W2321541738 abstract "Hydrogen sulfide (H 2 S) affects vascular resistance; however, its effect on the hepatic microcirculation has not been investigated. Hepatic sinusoidal perfusion is dysregulated during sepsis, contributing to liver injury. Therefore, the present study determined the effect of H 2 S on the hepatic microcirculation and the contribution of endogenous H 2 S to hepatic microcirculatory dysfunction in an endotoxin model of sepsis. Portal infusion of H 2 S increased portal pressure in vivo (6.8 ± 0.2 mmHg before H 2 S vs. 8.6 ± 0.8 mmHg peak during H 2 S infusion, P < 0.05). Using intravital microscopy, we observed decreased sinusoidal diameter (6.2 ± 0.27 μm before H 2 S vs. 5.7 ± 0.3 μm after H 2 S, P < 0.05) and increased sinusoidal heterogeneity during H 2 S infusion ( P < 0.05) and net constriction. Since hepatic H 2 S levels are elevated during sepsis, we used the cystathionine γ lyase inhibitor dl-propargylglycine (PAG) to determine the contribution of H 2 S to the hypersensitization of the sinusoid to the vasoconstrictor effect of endothelin-1 (ET-1). PAG treatment significantly attenuated the sinusoidal sensitization to ET-1 in endotoxin-treated animals. ET-1 infusion increased portal pressure to 175% of baseline in endotoxemic animals, which was reduced to 143% following PAG treatment ( P < 0.05). PAG abrogated the increase in sinusoidal constriction after ET-1 infusion in LPS-treated rats (30.9% reduction in LPS rats vs. 11.6% in PAG/LPS rats, P < 0.05). Moreover, PAG treatment significantly attenuated the increase in NADH fluorescence following ET-1 exposure during endotoxemia (61 grayscale units LPS vs. 21 units in PAG/LPS, P < 0.05), suggesting an improvement in hepatic oxygen availability. This study is the first to demonstrate a vasoconstrictor action of H 2 S on the hepatic sinusoid and provides a possible mechanism for the protective effect of PAG treatment during sepsis." @default.
• W2321541738 created "2016-06-24" @default.
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• W2321541738 date "2013-06-15" @default.
• W2321541738 modified "2023-09-27" @default.
• W2321541738 title "Hydrogen sulfide modulates sinusoidal constriction and contributes to hepatic micorcirculatory dysfunction during endotoxemia" @default.
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• W2321541738 doi "https://doi.org/10.1152/ajpgi.00395.2012" @default.
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