title: The effect of three angiotensin-converting enzyme inhibitors on kynurenic acid production in rat kidney in vitro.
abstract: BACKGROUND
  The renin-angiotensin system (RAS) is commonly known to regulate blood pressure, water and electrolyte homeostasis, however it also exerts paracrine and autocrine actions on the kidney. Angiotensin-converting enzyme inhibitors (ACE-Is), alongside their hypotensive properties, have been shown to decrease kidney function decline in animal models of nephropathy. Glutamate (GLU) is the main stimulatory neurotransmitter in the central nervous system, however its importance in the periphery should also be considered. Activation of renal GLU receptors has been linked to normal kidney function and also renal injury. The wide spectrum GLU receptor antagonist kynurenic acid (KYNA) possesses neuroprotective and central hypotensive effects, however its actions outside the brain are less well recognized. KYNA is a tryptophan metabolite synthesized from kynurenine by kynurenine aminotransferases (KATs). The purpose of this study was to examine the influence of three ACE-Is: lisinopril, perindopril and ramipril on KYNA production and KATs activity in rat kidney in vitro.
  
  
  METHODS
  The effect of ACE-Is on KYNA production and KATs activity was examined in rat kidney homogenates. KYNA was detected by high-performance liquid chromatography (HPLC) and quantified fluorometrically.
  
  
  RESULTS
  All examined ACE-Is: lisinopril, perindopril and ramipril decreased KYNA production in rat kidney in vitro. KAT I activity was decreased by lisinopril and ramipril whereas the activity of KAT II was lowered by ramipril.
  
  
  CONCLUSIONS
  Our study shows that ACE-Is can decrease KYNA production in rat kidney in vitro. Further studies are required to determine the clinical importance of the inhibitory action of ACE-Is on KYNA synthesis in the kidney.
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Lublin, Poland. Electronic address: izabela.zakrocka@umlub.pl.
authors.forename: Izabela
authors.initials: I
authors.lastname: Zakrocka
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Lublin, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kocki
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Lublin, Poland.
authors.forename: Waldemar A
authors.initials: WA
authors.lastname: Turski
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007736:Kynurenic Acid / Q000378:metabolism*; D017706:Lisinopril / Q000494:pharmacology; D008297:Male; D020913:Perindopril / Q000494:pharmacology; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000637:Transaminases / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D017706:Lisinopril; D000637:Transaminases; C021481:kynurenine-oxoglutarate transaminase; D007736:Kynurenic Acid; D017257:Ramipril; D020913:Perindopril
keywords: Angiotensin-converting enzyme inhibitors; Kidney angiotensin-converting enzyme; Kynurenic acid; Renin-angiotensin system