Hydrogen sulfide ameliorates hypertension and vascular dysfunction induced by insulin resistance in rats by reducing oxidative stress and activating eNOS

• Published in: European journal of pharmacology Vol. 963; p. 176266
• Main Authors: Silva-Velasco, Diana L, Hong, Enrique, Beltran-Ornelas, Jesus H, Sánchez-López, Araceli, Huerta de la Cruz, Saúl, Tapia-Martínez, Jorge A, Gomez, Carolina B, Centurión, David
• Format: Journal Article
• Language: English
• Published: Netherlands 15.01.2024
• Subjects: Animals; Cystathionine gamma-Lyase - antagonists & inhibitors; Cystathionine gamma-Lyase - metabolism; Cysteine - metabolism; Cysteine - pharmacology; Cysteine - therapeutic use; Diabetes Mellitus, Type 2 - complications; Hydrogen Sulfide - metabolism; Hydrogen Sulfide - pharmacology; Hydrogen Sulfide - therapeutic use; Hypertension - drug therapy; Hypertension - metabolism; Insulin Resistance - physiology; Nitric Oxide Synthase Type III - metabolism; Oxidative Stress - drug effects; Rats; Reactive Oxygen Species; Hydrogen sulfide; Insulin resistance; Vascular dysfunction; Vasorelaxation; Vasoconstriction
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2023.176266

Hydrogen sulfide (H S) is a gasotransmitter implied in metabolic diseases, insulin resistance, obesity, and type 2 Diabetes Mellitus. This study aimed to determine the effect of chronic administration of sodium hydrosulfide (NaHS; inorganic H S donor), L-Cysteine (L-Cys; substrate of H S producing enzymes) and DL-Propargylglycine (DL-PAG; cystathionine-gamma-lyase inhibitor) on the vascular dysfunction induced by insulin resistance in rat thoracic aorta. For this purpose, 72 animals were divided into two main sets that received: 1) tap water (control group; n = 12); and 2) fructose 15% w/v in drinking water [insulin resistance group (IR); n = 60] for 20 weeks. After 16 weeks, the group 2 was divided into five subgroups (n = 12 each), which received daily i. p. injections during 4 weeks of: 1) non-treatment (control); 2) vehicle (phosphate buffer saline; PBS, 1 ml/kg); 3) NaHS (5.6 mg/kg); 4) L-Cys (300 mg/kg); and (5) DL-PAG (10 mg/kg). Hemodynamic variables, metabolic variables, vascular function, ROS levels and the expression of p-eNOS and eNOS were determined. IR induced: 1) hyperinsulinemia; 2) increased HOMA-index; 3) decreased Matsuda index; 4) hypertension, vascular dysfunction, increased ROS levels; 5) increased iNOS, and 6) decreased CSE, p-eNOS and eNOS expression. Furthermore, IR did not affect contractile responses to norepinephrine. Interestingly, NaHS and L-Cys treatment, reversed IR-induced impairments and DL-PAG treatment decreased and increased the HOMA and Matsuda index, respectively. Taken together, these results suggest that NaHS and L-Cys decrease the metabolic and vascular alterations induced by insulin resistance by reducing oxidative stress and activating eNOS. Thus, hydrogen sulfide may have a therapeutic application.