Interdependency of Cystathione γ-Lyase and Cystathione β-Synthase in Hydrogen Sulfide-Induced Blood Pressure Regulation in Rats

• Published in: American journal of hypertension 2012-01, Vol.25 (1), p.74-81
• Main Authors: Roy, Alexander, Khan, Abdul H., Islam, Mohammed T., Prieto, Minolfa C., Majid, Dewan S.A.
• Format: Article
• Language: English
• Subjects: Alkynes - pharmacology; Aminooxyacetic Acid - pharmacology; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Cardiology. Vascular system; Cystathionine beta-Synthase - antagonists & inhibitors; Cystathionine beta-Synthase - physiology; Cystathionine gamma-Lyase - antagonists & inhibitors; Cystathionine gamma-Lyase - physiology; Drug Combinations; Experimental diseases; Glomerular Filtration Rate - drug effects; Glycine - analogs & derivatives; Glycine - pharmacology; Hydrogen Sulfide - metabolism; Hydrogen Sulfide - pharmacology; Hypertension - physiopathology; Kidney; Kidney - enzymology; Male; Medical sciences; Rats; Rats, Sprague-Dawley; Renal Circulation - drug effects; Sodium - urine; Sulfates - urine
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1038/ajh.2011.149

Background Hydrogen sulfide (H2S), an endogenous vasoactive agent, is produced by cystathionine γ-lyase (CGL) and cystathionine β-synthase (CBS) enzymes. This study was conducted to evaluate the relative contribution of these enzymes in regulating systemic arterial pressure. Methods Sprague-Dawley rats were chronically treated with CGL inhibitor, DL-propargylglycine (PAG, 37.5mg/kg/day; intraperitoneally, i.p.) or CBS inhibitor, aminooxyacetic acid (AOA, 8.75mg/kg/day; i.p.) or in combination for 4 weeks and the effects on arterial pressure (tail-cuff plethysmography) and renal excretory function (24 h urine collections using metabolic cages) were assessed once in a week. Changes in renal blood flow (RBF; Ultrasonic flowmetry) and glomerular filtration rate (GFR; Inulin clearance) were assessed in acute experiments in anesthetized rats at the end of treatment period. Results Compared to vehicle treated control group, only the rats with combination therapy showed a decrease in urinary sulfate excretion rate (248 ± 47 vs. 591 ± 70nmol/24h; marker for endogenous H2S level) which was associated with an increase in mean arterial pressure (MAP; 130 ± 2 vs. 99 ± 2mmHg). Urine flow and sodium excretion were also increased in combination group as consequent to the increase in MAP. GFR did not alter due to these treatments but RBF was lowered (4 ± 0.3 vs. 7 ± 0.4ml/min/g) only in the combination group compared to the control group. Conclusion These findings indicate that a deficiency in one enzyme's activity could be compensated by the activity of the other to maintain the endogenous H2S level, the deficiency of which modulates systemic and renal vascular resistances leading to the development of hypertension.