Biochem Pharmacol. 2026 Feb;244:117608. doi: 10.1016/j.bcp.2025.117608. Epub 2025 Dec 5.
ABSTRACT
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. CKD 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.
PMID:41352564 | DOI:10.1016/j.bcp.2025.117608