title: 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.
abstract: 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.
authors: Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Department of Pathophysiology, Second Faculty of Medicine, Charles University, Prague, Czech Republic. luce@medicon.cz.
authors: A
authors: A
authors: Sporková
authors: Z
authors: Z
authors: Husková
authors: P
authors: P
authors: Škaroupková
authors: N
authors: N
authors: Rami Reddy
authors: J R
authors: JR
authors: Falck
authors: J
authors: J
authors: Sadowski
authors: L
authors: L
authors: Červenka
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000235:genetics / Q000503:physiopathology*; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D012083:Renin / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: C535029:Ren2 protein, rat; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D012083:Renin; D015126:8,11,14-Eicosatrienoic Acid; D000109:Acetylcholine; D009638:Norepinephrine