title: Orally active epoxyeicosatrienoic acid analog does not exhibit antihypertensive and reno- or cardioprotective actions in two-kidney, one-clip Goldblatt hypertensive rats.
abstract: This study examined the effects of a novel orally active 14,15-epoxyeicosatrienoic acid analog (EET-A) on blood pressure (BP) and myocardial infarct size (IS) in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats during sustained phase of hypertension. Between days 31 and 35 after clip placement the rats were treated with EET-A and BP was monitored by radiotelemetry; sham-operated normotensive rats were used as controls. Tissue concentrations of epoxyeicosatrienoic acids served as a marker of production of epoxygenase metabolites. The rats were subjected to acute myocardial ischemia/reperfusion (I/R) injury and IS was determined. We found that EET-A treatment did not lower BP in 2K1C rats and did not alter availability of biologically active epoxygenase metabolites in 2K1C or in sham-operated rats. The myocardial IS was significantly smaller in untreated 2K1C rats as compared with normotensive controls and EET-A reduced it in controls but not in 2K1C rats. Our findings suggest that during the phase of sustained hypertension 2K1C Goldblatt hypertensive rats exhibit increased cardiac tolerance to I/R injury as compared with normotensive controls, and that in this animal model of human renovascular hypertension short-term treatment with EET-A does not induce any antihypertensive and cardioprotective actions.
authors: Department of Developmental Cardiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic. Electronic address: Petra.Alanova@fgu.cas.cz.
authors: Petra
authors: P
authors: Alánová
authors: Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. Electronic address: zuzka.huska@email.cz.
authors: Zuzana
authors: Z
authors: Husková
authors: Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. Electronic address: likp@medicon.cz.
authors: Libor
authors: L
authors: Kopkan
authors: Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. Electronic address: alhc@medicon.cz.
authors: Alexandra
authors: A
authors: Sporková
authors: Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. Electronic address: savr@medicon.cz.
authors: Šárka
authors: Š
authors: Jíchová
authors: Department of Developmental Cardiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic; Department of Pharmacology and Toxicology, Medical College of Wisconsin, WI, USA. Electronic address: neckar@biomed.cas.cz.
authors: Jan
authors: J
authors: Neckář
authors: Department of Pharmacology and Toxicology, Medical College of Wisconsin, WI, USA. Electronic address: jdimig@mcw.edu.
authors: John D
authors: JD
authors: Imig
authors: Department of Developmental Cardiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic. Electronic address: kolar@biomed.cas.cz.
authors: Martina
authors: M
authors: Klevstig
authors: Department of Developmental Cardiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic. Electronic address: kolar@biomed.cas.cz.
authors: František
authors: F
authors: Kolář
authors: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: J.Falck@UTSouthwestern.edu.
authors: N
authors: N
authors: Rami Reddy
authors: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: J.Falck@UTSouthwestern.edu.
authors: John R
authors: JR
authors: Falck
authors: Department of Renal and Body Fluid Physiology, M. Mossakowski Medical Research Centre, Polish Academy of Science, Warsaw, Poland. Electronic address: sajan0@op.pl.
authors: Janusz
authors: J
authors: Sadowski
authors: Department of Pharmacology, Kagawa University, Kagawa, Japan. Electronic address: akira@kms.ac.jp.
authors: Akira
authors: A
authors: Nishiyama
authors: Section of Nephrology, Medical Polyclinic, Department of Medicine, University of Bonn, Bonn, Germany. Electronic address: hkramer@uni-bonn.de.
authors: Herbert J
authors: HJ
authors: Kramer
authors: Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. Electronic address: vome@medicon.cz.
authors: Vojtěch
authors: V
authors: Melenovský
authors: Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. Electronic address: cerl@medicon.cz.
authors: Lenka
authors: L
authors: Červenková
authors: Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Department of Pathology, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic.
authors: Petr
authors: P
authors: Kujal
authors: Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Department of Pathology, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic.
authors: Zdenka
authors: Z
authors: Vernerová
authors: Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Department of Pathophysiology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address: luce@medicon.cz.
authors: Luděk
authors: L
authors: Červenka
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory / Q000379:methods; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013686:Telemetry; D013997:Time Factors
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D015126:8,11,14-Eicosatrienoic Acid
keywords: 14,15-Epoxyeicosatrienoic acid analog; Myocardial ischemia/reperfusion injury; Renin−angiotensin system; Renovascular hypertension