CHRONIC BLOCKADE OF ENDOGENOUS FORMATION OF HYDROGEN SULFIDE CAUSED INCREASE IN SYSTEMIC BLOOD PRESSURE IN RATS

Abstract

Hydrogen sulfide (H2S), an endogenous vasodilator, is produced by two enzymes; cystathionine γ‐lyase (CSE) and cystathionine β‐synthase (CBS). In this study, the effects of chronic inhibition of CSE by DL‐propargylglycine (37.5 mg/kg/day; ip) and CBS by aminoxyacetic acid (8.8 mg/kg/day; ip) given either alone or in combination for 4 weeks on systemic blood pressure (SBP) and renal function were examined in rats (n=6 in each group). Prior to the start and then every 7th day during treatment period, SBP was measured by tail‐cuff method and 24 hr urine collections were made using metabolic cages. Urinary excretion rate of sulfate (USV; marker for endogenous H2S level) was determined by a colorimetric assay. At the end of treatment period, rats were subjected to acute experiments under anesthesia for determination of renal blood flow (RBF; Transonic flow‐probe) and glomerular filtration rate (GFR; inulin clearance). Compared to vehicle treated group, only the combined therapy group showed a decrease in USV (553±71 vs 248±50 nmol/24hr) and an increase in mean SBP (107±3 vs 130±2 mmHg) with its consequent increase in sodium excretion (4±1 vs 13±3 mmol/24hr). This group with combined therapy also showed a decrease in RBF (7±0.4 vs 4±0.3 mL/min/g) but not appreciably in GFR (1.0±0.1 vs 0.9±0.03 mL/min/g). These data suggest that a decrease in endogenous H2S production exerts direct vascular effect leading to an increase in SBP.