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

doi:10.1016/j.vph.2015.08.013

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

Biochemistry

Research output: Contribution to journal › Article › peer-review

12 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 language	English (US)
Pages (from-to)	45-56
Number of pages	12
Journal	Vascular Pharmacology
Volume	73
DOIs	https://doi.org/10.1016/j.vph.2015.08.013
State	Published - 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

Access to Document

10.1016/j.vph.2015.08.013

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

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, 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, vol. 73, pp. 45-56. https://doi.org/10.1016/j.vph.2015.08.013

@article{375d6ae226fe4b7399cd4dddd514cda1,

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.",

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

author = "Petra Al{\'a}nov{\'a} and Zuzana Huskov{\'a} and Libor Kopkan and Alexandra Sporkov{\'a} and {\v S}{\'a}rka J{\'i}chov{\'a} and Jan Neck{\'a}{\v r} and Imig, {John D.} and Martina Klevstig and Franti{\v s}ek Kol{\'a}{\v r} and {Rami Reddy}, N. and Falck, {J R} and Janusz Sadowski and Akira Nishiyama and Kramer, {Herbert J.} and Vojt{\v e}ch Melenovsk{\'y} and Lenka {\v C}ervenkov{\'a} and Petr Kujal and Zdenka Vernerov{\'a} and Lud{\v e}k {\v C}ervenka",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = oct,

day = "1",

doi = "10.1016/j.vph.2015.08.013",

language = "English (US)",

volume = "73",

pages = "45--56",

journal = "Vascular Pharmacology",

issn = "1537-1891",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Orally active epoxyeicosatrienoic acid analog does not exhibit antihypertensive and reno- or cardioprotective actions in two-kidney, one-clip Goldblatt hypertensive rats

AU - Alánová, Petra

AU - Husková, Zuzana

AU - Kopkan, Libor

AU - Sporková, Alexandra

AU - Jíchová, Šárka

AU - Neckář, Jan

AU - Imig, John D.

AU - Klevstig, Martina

AU - Kolář, František

AU - Rami Reddy, N.

AU - Falck, J R

AU - Sadowski, Janusz

AU - Nishiyama, Akira

AU - Kramer, Herbert J.

AU - Melenovský, Vojtěch

AU - Červenková, Lenka

AU - Kujal, Petr

AU - Vernerová, Zdenka

AU - Červenka, Luděk

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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.

AB - 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.

KW - 14,15-Epoxyeicosatrienoic acid analog

KW - Myocardial ischemia/reperfusion injury

KW - Renin-angiotensin system

KW - Renovascular hypertension

UR - http://www.scopus.com/inward/record.url?scp=84941741068&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941741068&partnerID=8YFLogxK

U2 - 10.1016/j.vph.2015.08.013

DO - 10.1016/j.vph.2015.08.013

M3 - Article

C2 - 26304700

AN - SCOPUS:84941741068

SN - 1537-1891

VL - 73

SP - 45

EP - 56

JO - Vascular Pharmacology

JF - Vascular Pharmacology

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this