Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 857-873 |
| Number of pages | 17 |
| Journal | Physiological Research |
| Volume | 64 |
| Issue number | 6 |
| State | Published - 2015 |
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Keywords
- Aorto-caval fistula
- Congestive heart failure
- Epoxyeicosatrienoic acids
- Renin-angiotensin system
- Soluble epoxide hydrolase
ASJC Scopus subject areas
- Medicine(all)
- Physiology
Cite this
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. / Červenka, L.; Melenovský, V.; Husková, Z.; Sporková, A.; Bürgelová, M.; Škaroupková, P.; Hwang, S. H.; Hammock, B. D.; Imig, J. D.; Sadowski, J.
In: Physiological Research, Vol. 64, No. 6, 2015, p. 857-873.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Červenka, L.
AU - Melenovský, V.
AU - Husková, Z.
AU - Sporková, A.
AU - Bürgelová, M.
AU - Škaroupková, P.
AU - Hwang, S. H.
AU - Hammock, B. D.
AU - Imig, J. D.
AU - Sadowski, J.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Aorto-caval fistula
KW - Congestive heart failure
KW - Epoxyeicosatrienoic acids
KW - Renin-angiotensin system
KW - Soluble epoxide hydrolase
UR - http://www.scopus.com/inward/record.url?scp=84983099949&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84983099949&partnerID=8YFLogxK
M3 - Article
C2 - 26047375
AN - SCOPUS:84983099949
VL - 64
SP - 857
EP - 873
JO - Physiological Research
JF - Physiological Research
SN - 0862-8408
IS - 6
ER -