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

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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

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Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Physiology

Cite this

Alánová, P., Husková, Z., Kopkan, L., Sporková, A., Jíchová, Š., Neckář, J., Imig, J. D., Klevstig, M., Kolář, F., Rami Reddy, N., Falck, J. R., Sadowski, J., Nishiyama, A., Kramer, H. J., Melenovský, V., Červenková, L., Kujal, P., Vernerová, Z., & Červenka, L. (2015). Orally active epoxyeicosatrienoic acid analog does not exhibit antihypertensive and reno- or cardioprotective actions in two-kidney, one-clip Goldblatt hypertensive rats. Vascular Pharmacology, 73, 45-56. https://doi.org/10.1016/j.vph.2015.08.013