Exogenous hydrogen sulfide inhibits the progression of vascular dysfunction and hypertension mediated by the renin-angiotensin system in chronic kidney disease

Chronic kidney disease (CKD) overactivates the renin-angiotensin system (RAS), causing vascular dysfunction and hypertension. Additionally, hydrogen sulfide (H₂S) is a gasotransmitter that modulates the cardiovascular system by attenuating the RAS. Therefore, this study aimed to investigate the effects of chronic administration of sodium hydrosulfide (NaHS, an exogenous H₂S donor) on RAS-mediated vascular responses, oxidative stress, and progression of hypertension in rats with CKD. Thirty-two normotensive male Wistar rats were divided into four groups (n = 8): 1) sham + vehicle (1 mL/kg/d, 100 mM of phosphate buffer, PBS), 2) sham + NaHS (5.6 mg/kg/d), 3) CKD induced by 5/6 nephrectomy + vehicle, and 4) CKD + NaHS. One week after surgery, pharmacological treatments began and were administered intraperitoneally daily for six weeks. Hemodynamic variables, renal function, and H₂S serum levels were assessed. Additionally, H₂S formation, oxidative stress, and the expression of AT₁, AT₂, Mas receptors, and H₂S-synthesizing enzymes, along with vascular responses to angiotensin (1-7), angiotensin II and H₂S were assessed in the thoracic aorta. CKS impairs: 1) RAS-mediated vascular responses; 2) downregulates Mas receptor expression; 3) upregulates AT₁ and AT₂ receptor expression; 4) increases H₂S-mediated vascular response, 5) decreases H₂S levels, tissue production of H₂S and the expression of the producing enzymes; and 6) induces oxidative stress. Interestingly, NaHS treatment prevented CKD-induced impairments. In conclusion, NaHS administration protects against RAS-mediated vascular dysfunction and progression of hypertension by preventing alterations in AT₁, AT₂, Mas receptors, H₂S-synthesizing enzymes, and oxidative stress.