Chronic Blockade of Endogenous Formation of Hydrogen Sulfide Caused Increase in Systemic Blood Pressure of Rats

Hydrogen sulfide (H2S) is produced endogenously from L-cysteine by the actions of enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS). The role of these enzymes in the regulation of systemic blood pressure (SBP) is not yet clearly defined. In this study, we have examined the effect of chronic deficiency of endogenous H2S, which was induced by inhibitors of CSE and CBS, on SBP and renal parameters in rats. Sprague-Dawley rats were treated with inhibitors of CSE (DL-propargylglycine, PAG; 37.5 mg/kg/day i.p.) and CBS (aminoxyacetic acid, AOA; 8.75 mg/kg/day i.p.) formation. These two inhibitors were administered to different sample groups alone and in combination. SBP was measured by tail-cuff plethysmography before any H2Sinhibitors were administered, and then this was repeated once every week during treatment period. 24hr urine collection with metabolic cages was done within the same timeframe and schedule. Concentrations of urinary sodium and sulfate (marker of H2S) were measured using flame photometry and colorimetry, respectively. After a three week period of drug administration, the only group to show significant decrease in urinary excretion of sulfate (USV) and an increase in mean SBP was the group treated with a combination of CBS and CSE inhibitors. There were also increases in urine flow (V) and sodium excretion (UNaV) in this group, which can be attributed to consequent pressure dependent effects on renal excretory function. The findings from the 3 week period of treatment are summarized in the following Table: