Vasoactive Effects of H2S in High-Calorie Diet-Induced Metabolic Syndrome

Metabolic syndrome (MS), a global problem of the 21st century, is characterized by hypertension, which is caused by the predominance of vasoconstriction over vasodilation. Hydrogen sulfide (H2S) is a recognized endogenous gas signaling molecule that has a variety of biological effects, including changes in vascular tone. The aim of this work was to study changes in contractile activity in isolated rat aorta in response to sodium hydrosulfide (NaHS), an H2S donor, and endogenous H2S during metabolic disturbances induced by a high-calorie (Western) diet. The study was performed on mature male Wistar rats. The diet resulted in the development of metabolic disturbances typical for MS. The results of a myographic study of thoracic aortic segments indicated that, in both the control and experimental groups, the administration of NaHS, depending on its concentration, resulted in bimodal effects, causing vasoconstriction at low concentrations and significantly more pronounced vasodilation at high concentrations. The effect of endogenous H2S depends on the state of perivascular adipose tissue and decreases in MS. Thus, the increase in H2S-induced vasodilation in MS is likely reflects a compensatory response to a decrease in endogenous H2S production. ATP-sensitive potassium channels play a leading role in mediating relaxation responses of aortic smooth muscle to H2S. However, their contribution to the development of vasodilation is less pronounced in MS, which is a consequence of changes in the involvement of other mechanisms. A decrease in H2S-induced vasoconstriction in MS, caused by increased superoxide anion production, may be one of these mechanisms. The interaction of various pathways for the implementation of H2S-induced vasorelaxation in metabolic disorders represents an important direction for further research to prevent the development of vascular diseases, including by regulating vascular tone.