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Description
| - Alterations in renal function contribute to Goldblatt two-kidney, one-clip (2K1C) hypertension. A previous study indicated that bioavailability of cytochrome P-450 metabolites epoxyeicosatrienoic acids (EETs) is decreased while that of 20-hydroxyeicosatetraenoic acids (20-HETE) is increased in this model. We utilized the inhibitor of soluble epoxide hydrolase cis-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (c-AUCB) and HET-0016, the inhibitor of 20-HETE production, to study the role of EETs and 20-HETE in the regulation of renal function. Chronic c-AUCB treatment significantly decreased systolic blood pressure (SBP) (133 ? 1 vs. 163 ? 3 mmHg) and increased sodium excretion (1.23 ? 0.10 vs. 0.59 ? 0.03 mmol/day) in 2K1C rats. HET-0016 did not affect SBP and sodium excretion. In acute experiments, renal blood flow (RBF) was decreased in 2K1C rats (5.0 ? 0.2 vs. 6.9 ? 0.2 ml?min(-1)?g(-1)). c-AUCB normalized RBF in 2K1C rats (6.5 ? 0.6 ml?min(-1)?g(-1)). HET-0016 also increased RBF in 2K1C rats (5.8 ? 0.2 ml?min(-1)?g(-1)). Although RBF and glomerular filtration rate (GFR) remained stable in normotensive rats during renal arterial pressure (RAP) reductions, both were significantly reduced at 100 mmHg RAP in 2K1C rats. c-AUCB did not improve autoregulation but increased RBF at all RAPs and shifted the pressure-natriuresis curve to the left. HET-0016-treated 2K1C rats exhibited impaired autoregulation of RBF and GFR. Our data indicate that c-AUCB displays antihypertensive properties in 2K1C hypertension that are mediated by an improvement of RBF and pressure natriuresis. While HET-0016 enhanced RBF, its anti-natriuretic effect likely prevented it from producing a blood pressure-lowering effect in the 2K1C model.
- Alterations in renal function contribute to Goldblatt two-kidney, one-clip (2K1C) hypertension. A previous study indicated that bioavailability of cytochrome P-450 metabolites epoxyeicosatrienoic acids (EETs) is decreased while that of 20-hydroxyeicosatetraenoic acids (20-HETE) is increased in this model. We utilized the inhibitor of soluble epoxide hydrolase cis-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (c-AUCB) and HET-0016, the inhibitor of 20-HETE production, to study the role of EETs and 20-HETE in the regulation of renal function. Chronic c-AUCB treatment significantly decreased systolic blood pressure (SBP) (133 ? 1 vs. 163 ? 3 mmHg) and increased sodium excretion (1.23 ? 0.10 vs. 0.59 ? 0.03 mmol/day) in 2K1C rats. HET-0016 did not affect SBP and sodium excretion. In acute experiments, renal blood flow (RBF) was decreased in 2K1C rats (5.0 ? 0.2 vs. 6.9 ? 0.2 ml?min(-1)?g(-1)). c-AUCB normalized RBF in 2K1C rats (6.5 ? 0.6 ml?min(-1)?g(-1)). HET-0016 also increased RBF in 2K1C rats (5.8 ? 0.2 ml?min(-1)?g(-1)). Although RBF and glomerular filtration rate (GFR) remained stable in normotensive rats during renal arterial pressure (RAP) reductions, both were significantly reduced at 100 mmHg RAP in 2K1C rats. c-AUCB did not improve autoregulation but increased RBF at all RAPs and shifted the pressure-natriuresis curve to the left. HET-0016-treated 2K1C rats exhibited impaired autoregulation of RBF and GFR. Our data indicate that c-AUCB displays antihypertensive properties in 2K1C hypertension that are mediated by an improvement of RBF and pressure natriuresis. While HET-0016 enhanced RBF, its anti-natriuretic effect likely prevented it from producing a blood pressure-lowering effect in the 2K1C model. (en)
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Title
| - Role of cytochrome P-450 metabolites in the regulation of renal function and blood pressure in 2-kidney 1-clip hypertensive rats.
- Role of cytochrome P-450 metabolites in the regulation of renal function and blood pressure in 2-kidney 1-clip hypertensive rats. (en)
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skos:prefLabel
| - Role of cytochrome P-450 metabolites in the regulation of renal function and blood pressure in 2-kidney 1-clip hypertensive rats.
- Role of cytochrome P-450 metabolites in the regulation of renal function and blood pressure in 2-kidney 1-clip hypertensive rats. (en)
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skos:notation
| - RIV/00023001:_____/11:00002478!RIV12-MZ0-00023001
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http://linked.open...avai/riv/aktivita
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http://linked.open...avai/riv/aktivity
| - I, P(GC305/08/J006), P(GPP303/10/P170), P(KJB502030801), P(NS10499), P(NS9699), Z(MZ0IKEM2005)
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http://linked.open...iv/cisloPeriodika
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http://linked.open...vai/riv/dodaniDat
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http://linked.open...aciTvurceVysledku
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http://linked.open.../riv/druhVysledku
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http://linked.open...iv/duvernostUdaju
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http://linked.open...titaPredkladatele
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http://linked.open...dnocenehoVysledku
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http://linked.open...ai/riv/idVysledku
| - RIV/00023001:_____/11:00002478
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http://linked.open...riv/jazykVysledku
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http://linked.open.../riv/klicovaSlova
| - renovascular hypertenison; cytochrome P450 metabolites; epoxyeicosatrienoic acids; hydroxyeicosatrienoic acids; reanal functions; blood pressure; autoregulation; glomerular filtration rate; renal blood flow; c-AUCB; HET0016 (en)
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http://linked.open.../riv/klicoveSlovo
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http://linked.open...odStatuVydavatele
| - US - Spojené státy americké
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http://linked.open...ontrolniKodProRIV
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http://linked.open...i/riv/nazevZdroje
| - American journal of physiology. Regulatory, integrative and comparative physiology
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http://linked.open...in/vavai/riv/obor
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http://linked.open...ichTvurcuVysledku
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http://linked.open...cetTvurcuVysledku
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http://linked.open...vavai/riv/projekt
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http://linked.open...UplatneniVysledku
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http://linked.open...v/svazekPeriodika
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http://linked.open...iv/tvurceVysledku
| - Husková, Zuzana
- Červenka, Luděk
- Kopkan, Libor
- Sporková, Alexandra
- Hammock, Bruce D
- Imig, John D.
- Kramer, Herbert J.
- Hwang, Sug Hee
- Varcabová, Šárka
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http://linked.open...ain/vavai/riv/wos
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http://linked.open...n/vavai/riv/zamer
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issn
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number of pages
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http://bibframe.org/vocab/doi
| - 10.1152/ajpregu.00215.2010
|