Vasodilatory responses of renal interlobular arteries to epoxyeicosatrienoic acids analog are not enhanced in Ren-2 transgenic hypertensive rats: evidence against a role of direct vascular effects of epoxyeicosatrienoic acids in progression of experimental heart failure
Language English Country Czech Republic Media print-electronic
Document type Journal Article
PubMed
27782740
DOI
10.33549/physiolres.933350
PII: 933350
Knihovny.cz E-resources
- MeSH
- Acetylcholine pharmacology MeSH
- Hypertension genetics physiopathology MeSH
- Rats MeSH
- 8,11,14-Eicosatrienoic Acid analogs & derivatives chemistry pharmacology MeSH
- Kidney blood supply drug effects physiology MeSH
- Norepinephrine pharmacology MeSH
- Rats, Sprague-Dawley MeSH
- Rats, Transgenic MeSH
- Disease Progression MeSH
- Renal Circulation drug effects physiology MeSH
- Renin physiology MeSH
- Heart Failure genetics physiopathology MeSH
- Vasodilation drug effects physiology MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 14,15-epoxy-5,8,11-eicosatrienoic acid MeSH Browser
- Acetylcholine MeSH
- 8,11,14-Eicosatrienoic Acid MeSH
- Norepinephrine MeSH
- Ren2 protein, rat MeSH Browser
- Renin MeSH
Pathophysiological mechanisms underlying the development of renal dysfunction and progression of congestive heart failure (CHF) remain poorly understood. Recent studies have revealed striking differences in the role of epoxyeicosatrienoic acids (EETs), active products of cytochrome P-450-dependent epoxygenase pathway of arachidonic acid, in the progression of aorto-caval fistula (ACF)-induced CHF between hypertensive Ren-2 renin transgenic rats (TGR) and transgene-negative normotensive Hannover Sprague-Dawley (HanSD) controls. Both ACF TGR and ACF HanSD strains exhibited marked intrarenal EETs deficiency and impairment of renal function, and in both strains chronic pharmacologic inhibition of soluble epoxide hydrolase (sEH) (which normally degrades EETs) normalized EETs levels. However, the treatment improved the survival rate and attenuated renal function impairment in ACF TGR only. Here we aimed to establish if the reported improved renal function and attenuation of progression of CHF in ACF TGR observed after she blockade depends on increased vasodilatory responsiveness of renal resistance arteries to EETs. Therefore, we examined the responses of interlobar arteries from kidneys of ACF TGR and ACF HanSD rats to EET-A, a new stable 14,15-EET analog. We found that the arteries from ACF HanSD kidneys rats exhibited greater vasodilator responses when compared to the ACF TGR arteries. Hence, reduced renal vasodilatory responsiveness cannot be responsible for the lack of beneficial effects of chronic sEH inhibition on the development of renal dysfunction and progression of CHF in ACF HanSD rats.
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