期刊
PHYSIOLOGICAL RESEARCH
卷 64, 期 6, 页码 857-873出版社
ACAD SCIENCES CZECH REPUBLIC, INST PHYSIOLOGY
DOI: 10.33549/physiolres.932977
关键词
Congestive heart failure; Aorto-caval fistula; Renin-angiotensin system; Epoxyeicosatrienoic acids; Soluble epoxide hydrolase
类别
资金
- Internal Grant Agency of the Ministry of Health the Czech Republic [NT/14012-3/2013]
- Ministry of Health of the Czech Republic [00023001]
- European Commission within the Operational Program Prague-Competitiveness
- project CEVKOON [CZ.2.16/3.1.00/22126]
- NIH [DK38226]
- NIEHS Supported Basic Research Program
- NIEHS [R01 ES02710, R01 ES013933, P42 ES013933]
- West Coast Center [U24 DK097154]
- Internal Grant Agency of Health the Czech Republic [NT14050-3/2013, NT 14250-3/2013]
- Grant Agency of Czech Republic [15-14200S]
- Czech Ministry of Education [MSMT-LK12052-KONTAKT II]
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.
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