Interdependency of cystathione γ-lyase and cystathione β-synthase in hydrogen sulfide-induced blood pressure regulation in rats. Am J Hypertens 2012 Jan;25(1):74-81
Date
08/26/2011Pubmed ID
21866187Pubmed Central ID
PMC3258007DOI
10.1038/ajh.2011.149Scopus ID
2-s2.0-83655163852 (requires institutional sign-in at Scopus site) 62 CitationsAbstract
BACKGROUND: Hydrogen sulfide (H(2)S), 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, 37.5 mg/kg/day; intraperitoneally, i.p.) or CBS inhibitor, aminooxyacetic acid (AOA, 8.75 mg/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 ± 70 nmol/24 h; marker for endogenous H(2)S level) which was associated with an increase in mean arterial pressure (MAP; 130 ± 2 vs. 99 ± 2 mm Hg). 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 ± 0.4 ml/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 H(2)S level, the deficiency of which modulates systemic and renal vascular resistances leading to the development of hypertension.
Author List
Roy A, Khan AH, Islam MT, Prieto MC, Majid DSMESH terms used to index this publication - Major topics in bold
AlkynesAminooxyacetic Acid
Animals
Blood Pressure
Cystathionine beta-Synthase
Cystathionine gamma-Lyase
Drug Combinations
Glomerular Filtration Rate
Glycine
Hydrogen Sulfide
Hypertension
Kidney
Male
Rats
Rats, Sprague-Dawley
Renal Circulation
Sodium
Sulfates