Orally active epoxyeicosatrienoic acid analog does not exhibit antihypertensive and reno- or cardioprotective actions in two-kidney, one-clip Goldblatt hypertensive rats
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
DK38226
NIDDK NIH HHS - United States
PubMed
26304700
DOI
10.1016/j.vph.2015.08.013
PII: S1537-1891(15)00199-8
Knihovny.cz E-resources
- Keywords
- 14,15-Epoxyeicosatrienoic acid analog, Myocardial ischemia/reperfusion injury, Renin−angiotensin system, Renovascular hypertension,
- MeSH
- Blood Pressure Monitoring, Ambulatory methods MeSH
- Administration, Oral MeSH
- Time Factors MeSH
- Myocardial Infarction metabolism pathology prevention & control MeSH
- Glycogen Synthase Kinase 3 metabolism MeSH
- Glycogen Synthase Kinase 3 beta MeSH
- Blood Pressure drug effects MeSH
- 8,11,14-Eicosatrienoic Acid administration & dosage analogs & derivatives MeSH
- Hydroxyeicosatetraenoic Acids metabolism MeSH
- Kidney drug effects metabolism pathology MeSH
- Disease Models, Animal MeSH
- Myocardium metabolism pathology MeSH
- Rats, Sprague-Dawley MeSH
- Proto-Oncogene Proteins c-akt metabolism MeSH
- Renin-Angiotensin System drug effects MeSH
- Hypertension, Renovascular drug therapy metabolism physiopathology MeSH
- Myocardial Reperfusion Injury metabolism pathology prevention & control MeSH
- Signal Transduction drug effects MeSH
- Telemetry MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Names of Substances
- 14,15-epoxy-5,8,11-eicosatrienoic acid MeSH Browser
- Glycogen Synthase Kinase 3 MeSH
- Glycogen Synthase Kinase 3 beta MeSH
- 8,11,14-Eicosatrienoic Acid MeSH
- Hydroxyeicosatetraenoic Acids MeSH
- Proto-Oncogene Proteins c-akt MeSH
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.
Department of Biochemistry University of Texas Southwestern Medical Center Dallas TX USA
Department of Cardiology Institute for Clinical and Experimental Medicine Prague Czech Republic
Department of Pharmacology and Toxicology Medical College of Wisconsin WI USA
Department of Pharmacology Kagawa University Kagawa Japan
Section of Nephrology Medical Polyclinic Department of Medicine University of Bonn Bonn Germany
References provided by Crossref.org
Sixty Years of Heart Research in the Institute of Physiology of the Czech Academy of Sciences
