Orally active epoxyeicosatrienoic acid analog does not exhibit antihypertensive and reno- or cardioprotective actions in two-kidney, one-clip Goldblatt hypertensive rats

Petra Alánová, Zuzana Husková, Libor Kopkan, Alexandra Sporková, Šárka Jíchová, Jan Neckář, John D. Imig, Martina Klevstig, František Kolář, N. Rami Reddy, J R Falck, Janusz Sadowski, Akira Nishiyama, Herbert J. Kramer, Vojtěch Melenovský, Lenka Červenková, Petr Kujal, Zdenka Vernerová, Luděk Červenka

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)45-56
Number of pages12
JournalVascular Pharmacology
Volume73
DOIs
StatePublished - Oct 1 2015

Keywords

  • 14,15-Epoxyeicosatrienoic acid analog
  • Myocardial ischemia/reperfusion injury
  • Renin-angiotensin system
  • Renovascular hypertension

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

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