Inhibition of soluble epoxide hydrolase does not improve the course of congestive heart failure and the development of renal dysfunction in rats with volume overload induced by aorto-caval fistula. Physiol Res 2015;64(6):857-73
Date
06/06/2015Pubmed ID
26047375Pubmed Central ID
PMC4984848DOI
10.33549/physiolres.932977Scopus ID
2-s2.0-84983099949 (requires institutional sign-in at Scopus site) 28 CitationsAbstract
The detailed mechanisms determining the course of congestive heart failure (CHF) and associated renal dysfunction remain unclear. In a volume overload model of CHF induced by creation of aorto-caval fistula (ACF) in Hannover Sprague-Dawley (HanSD) rats we explored the putative pathogenetic contribution of epoxyeicosatrienoic acids (EETs), active products of CYP-450 dependent epoxygenase pathway of arachidonic acid metabolism, and compared it with the role of the renin-angiotensin system (RAS). Chronic treatment with cis-4-[4-(3-adamantan-1-yl-ureido) cyclohexyloxy]benzoic acid (c-AUCB, 3 mg/l in drinking water), an inhibitor of soluble epoxide hydrolase (sEH) which normally degrades EETs, increased intrarenal and myocardial EETs to levels observed in sham-operated HanSD rats, but did not improve the survival or renal function impairment. In contrast, chronic angiotensin-converting enzyme inhibition (ACEi, trandolapril, 6 mg/l in drinking water) increased renal blood flow, fractional sodium excretion and markedly improved survival, without affecting left ventricular structure and performance. Hence, renal dysfunction rather than cardiac remodeling determines long-term mortality in advanced stage of CHF due to volume overload. Strong protective actions of ACEi were associated with suppression of the vasoconstrictor/sodium retaining axis and activation of vasodilatory/natriuretic axis of the renin-angiotensin system in the circulating blood and kidney tissue.
Author List
Červenka L, Melenovský V, Husková Z, Sporková A, Bürgelová M, Škaroupková P, Hwang SH, Hammock BD, Imig JD, Sadowski JMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic AcidAngiotensin I
Angiotensin II
Angiotensin-Converting Enzyme Inhibitors
Animals
Benzoates
Disease Models, Animal
Drug Evaluation, Preclinical
Epoxide Hydrolases
Epoxy Compounds
Heart Failure
Kidney
Male
Myocardium
Peptide Fragments
Random Allocation
Rats
Renal Insufficiency
Renin-Angiotensin System
Ultrasonography
Urea
