Orally active epoxyeicosatrienoic acid analog does not exhibit antihypertensive and reno- or cardioprotective actions in two-kidney, one-clip Goldblatt hypertensive rats. Vascul Pharmacol 2015 Oct;73:45-56
Date
08/26/2015Pubmed ID
26304700DOI
10.1016/j.vph.2015.08.013Scopus ID
2-s2.0-84941741068 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
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.
Author List
Alánová P, Husková Z, Kopkan L, Sporková A, Jíchová Š, Neckář J, Imig JD, Klevstig M, Kolář F, Rami Reddy N, Falck JR, Sadowski J, Nishiyama A, Kramer HJ, Melenovský V, Červenková L, Kujal P, Vernerová Z, Červenka LMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic AcidAdministration, Oral
Animals
Blood Pressure
Blood Pressure Monitoring, Ambulatory
Disease Models, Animal
Glycogen Synthase Kinase 3
Glycogen Synthase Kinase 3 beta
Hydroxyeicosatetraenoic Acids
Hypertension, Renovascular
Kidney
Male
Myocardial Infarction
Myocardial Reperfusion Injury
Myocardium
Proto-Oncogene Proteins c-akt
Rats, Sprague-Dawley
Renin-Angiotensin System
Signal Transduction
Telemetry
Time Factors