Increasing evidence supports the important role of H2S in renal physiology and the pathogenesis of kidney injury. Whether H2S regulates water metabolism in the kidney and the potential mechanism are still unknown. The present study was conducted to determine the role of H2S in urine concentration. Inhibition of both
cystathionine-γ-
lyase (CSE) and
cystathionine-β-synthase (CBS), 2 major
enzymes for endogenous H2S production, with
propargylglycine (PPG) and amino-oxyacetate (AOAA), respectively, caused increased urine output and reduced urine osmolality in mice that was associated with decreased expression of
aquaporin (AQP)-2 in the renal inner medulla. Mice treated with both PPG and AOAA developed a urine concentration defect in response to
dehydration that was accompanied by reduced AQP-2
protein expression. Inhibition of CSE alone was associated with a mild decrease in AQP-2
protein level in the renal medulla of heterozygous CBS mice.
GYY4137, a slow H2S donor, markedly improved urine concentration and prevented the down-regulation of renal AQP-2
protein expression in mice with
lithium-induced
nephrogenic diabetes insipidus (NDI).
GYY4137 significantly increased cAMP levels in cell lysates prepared from inner medullary collecting duct (IMCD)
suspensions. AQP-2
protein expression was also upregulated, but was significantly inhibited by the
adenyl cyclase inhibitor
MDL12330A or the
PKA inhibitor H89, but not the
vasopressin 2 receptor (V2R) antagonist
tolvaptan. Inhibition of endogenous H2S production impaired urine concentration in mice, whereas an exogenous H2S donor improved urine concentration in
lithium-induced NDI by increasing AQP-2 expression in the collecting duct principal cells. H2S upregulated AQP-2
protein expression, probably via the cAMP-PKA pathway.-Luo, R., Hu, S., Liu, Q., Han, M., Wang, F., Qiu, M., Li, S., Li, X., Yang, T., Fu, X., Wang, W., Li, C.
Hydrogen sulfide upregulates renal AQP-2
protein expression and promotes urine concentration.