title: Interdependency of cystathione γ-lyase and cystathione β-synthase in hydrogen sulfide-induced blood pressure regulation in rats.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Roy
authors.forename: Abdul H
authors.initials: AH
authors.lastname: Khan
authors.forename: Mohammed T
authors.initials: MT
authors.lastname: Islam
authors.forename: Minolfa C
authors.initials: MC
authors.lastname: Prieto
authors.forename: Dewan S A
authors.initials: DS
authors.lastname: Majid
mesh_terms: D000480:Alkynes / Q000494:pharmacology; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000502:physiology*; D004338:Drug Combinations; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013431:Sulfates / Q000652:urine
chemical_list: D000480:Alkynes; D004338:Drug Combinations; D013431:Sulfates; D000625:Aminooxyacetic Acid; C009055:propargylglycine; D012964:Sodium; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D005998:Glycine; D006862:Hydrogen Sulfide