Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Antihypertensive and renoprotective actions of soluble epoxide hydrolase inhibition in ANG II-dependent malignant hypertension are abolished by pretreatment with L-NAME

Zuzana Honetschlägerová, Kento Kitada, Zuzana Husková, Alexandra Sporková, Libor. Kopkan, Marcela Bürgelová, Šárka Varcabová, Akira Nishiyama, Sung Hee Hwang, Bruce D. Hammock, John D. Imig, Herbert J. Kramer, Petr Kujal, Zdenka Vernerová, Luděk Červenka

. 2013 ; 31 (2) : 321-332.

Language English Country England, Great Britain

Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc13031720

Grant support
NT11230 MZ0 CEP Register
NT12171 MZ0 CEP Register

OBJECTIVE: The present study was performed to investigate in a model of malignant hypertension if the antihypertensive actions of soluble epoxide hydrolase (sEH) inhibition are nitric oxide (NO)-dependent. METHODS: ANG II-dependent malignant hypertension was induced through dietary administration for 3 days of the natural xenobiotic indole-3-carbinol (I3C) in Cyp1a1-Ren-2 transgenic rats. Blood pressure (BP) was monitored by radiotelemetry and treatment with the sEH inhibitor [cis-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyl-oxy]-benzoic acid (c-AUCB)] was started 48 h before administration of the diet containing I3C. In separate groups of rats, combined administration of the sEH inhibitor and the nonspecific NO synthase inhibitor [Nω-nitro-L-arginine methyl ester (L-NAME)] on the course of BP in I3C-induced and noninduced rats were evaluated. In addition, combined blockade of renin-angiotensin system (RAS) was superimposed on L-NAME administration in separate groups of rats. After 3 days of experimental protocols, the rats were prepared for renal functional studies and renal concentrations of epoxyeicosatrienoic acids (EETs) and their inactive metabolites dihydroxyeicosatrienoic acids (DHETEs) were measured. RESULTS: Treatment with c-AUCB increased the renal EETs/DHETEs ratio, attenuated the increases in BP, and prevented the decreases in renal function and the development of renal damage in I3C-induced Cyp1a1-Ren-2 rats. The BP lowering and renoprotective actions of the treatment with the sEH inhibitor c-AUCB were completely abolished by concomitant administration of L-NAME and not fully rescued by double RAS blockade without altering the increased EETs/DHETEs ratio. CONCLUSION: Our current findings indicate that the antihypertensive actions of sEH inhibition in this ANG II-dependent malignant form of hypertension are dependent on the interactions of endogenous bioavailability of EETs and NO.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc13031720
003      
CZ-PrNML
005      
20191024105908.0
007      
ta
008      
131002s2013 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1097/HJH.0b013e32835b50aa $2 doi
035    __
$a (PubMed)23307303
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Honetschlägerová, Zuzana $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
245    10
$a Antihypertensive and renoprotective actions of soluble epoxide hydrolase inhibition in ANG II-dependent malignant hypertension are abolished by pretreatment with L-NAME / $c Zuzana Honetschlägerová, Kento Kitada, Zuzana Husková, Alexandra Sporková, Libor. Kopkan, Marcela Bürgelová, Šárka Varcabová, Akira Nishiyama, Sung Hee Hwang, Bruce D. Hammock, John D. Imig, Herbert J. Kramer, Petr Kujal, Zdenka Vernerová, Luděk Červenka
520    9_
$a OBJECTIVE: The present study was performed to investigate in a model of malignant hypertension if the antihypertensive actions of soluble epoxide hydrolase (sEH) inhibition are nitric oxide (NO)-dependent. METHODS: ANG II-dependent malignant hypertension was induced through dietary administration for 3 days of the natural xenobiotic indole-3-carbinol (I3C) in Cyp1a1-Ren-2 transgenic rats. Blood pressure (BP) was monitored by radiotelemetry and treatment with the sEH inhibitor [cis-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyl-oxy]-benzoic acid (c-AUCB)] was started 48 h before administration of the diet containing I3C. In separate groups of rats, combined administration of the sEH inhibitor and the nonspecific NO synthase inhibitor [Nω-nitro-L-arginine methyl ester (L-NAME)] on the course of BP in I3C-induced and noninduced rats were evaluated. In addition, combined blockade of renin-angiotensin system (RAS) was superimposed on L-NAME administration in separate groups of rats. After 3 days of experimental protocols, the rats were prepared for renal functional studies and renal concentrations of epoxyeicosatrienoic acids (EETs) and their inactive metabolites dihydroxyeicosatrienoic acids (DHETEs) were measured. RESULTS: Treatment with c-AUCB increased the renal EETs/DHETEs ratio, attenuated the increases in BP, and prevented the decreases in renal function and the development of renal damage in I3C-induced Cyp1a1-Ren-2 rats. The BP lowering and renoprotective actions of the treatment with the sEH inhibitor c-AUCB were completely abolished by concomitant administration of L-NAME and not fully rescued by double RAS blockade without altering the increased EETs/DHETEs ratio. CONCLUSION: Our current findings indicate that the antihypertensive actions of sEH inhibition in this ANG II-dependent malignant form of hypertension are dependent on the interactions of endogenous bioavailability of EETs and NO.
650    _2
$a angiotensin II $x fyziologie $7 D000804
650    _2
$a zvířata $7 D000818
650    _2
$a antihypertenziva $x farmakologie $x terapeutické užití $7 D000959
650    _2
$a krevní tlak $x účinky léků $7 D001794
650    _2
$a inhibitory enzymů $x farmakologie $7 D004791
650    _2
$a epoxid hydrolasy $x antagonisté a inhibitory $7 D004851
650    _2
$a hypertenze $x farmakoterapie $x patofyziologie $7 D006973
650    _2
$a ledviny $x účinky léků $x patofyziologie $7 D007668
650    _2
$a NG-nitroargininmethylester $x aplikace a dávkování $x farmakologie $x terapeutické užití $7 D019331
650    _2
$a synthasa oxidu dusnatého $x antagonisté a inhibitory $7 D019001
650    _2
$a krysa rodu Rattus $7 D051381
650    _2
$a potkani transgenní $7 D055647
650    _2
$a látky reagující s kyselinou thiobarbiturovou $x metabolismus $7 D017392
655    _2
$a časopisecké články $7 D016428
655    _2
$a Research Support, N.I.H., Extramural $7 D052061
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Kitada, Kento $u Department of Pharmacology, Kagawa University, Kagawa, Japan
700    1_
$a Husková, Zuzana, $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic $d 1978- $7 xx0074206
700    1_
$a Sporková, Alexandra $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic $7 xx0239945
700    1_
$a Kopkan, Libor $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic $7 xx0107287
700    1_
$a Bürgelová, Marcela, $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic $d 1967- $7 xx0160368
700    1_
$a Varcabová, Šárka $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
700    1_
$a Nishiyama, Akira $u Department of Pharmacology, Kagawa University, Kagawa, Japan
700    1_
$a Hwang, Sung Hee $u Department of Entomology and UCD Cancer Center, University of California, Davis, Calif., USA
700    1_
$a Hammock, Bruce D. $u Department of Entomology and UCD Cancer Center, University of California, Davis, Calif., USA
700    1_
$a Imig, John D. $u Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisc., USA
700    1_
$a Kramer, Herbert J. $u Section of Nephrology, Medical Policlinic, Department of Medicine, University of Bonn, Bonn, Germany
700    1_
$a Kujal, Petr $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Department of Pathology, 3rd Faculty of Medicine, Prague, Czech Republic $7 xx0244311
700    1_
$a Vernerová, Zdenka, $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Department of Pathology, 3rd Faculty of Medicine, Prague, Czech Republic $d 1960-2020 $7 jo2002104672
700    1_
$a Červenka, Luděk, $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Department of Physiology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic $d 1967- $7 xx0037105
773    0_
$w MED00002723 $t Journal of hypertension $x 1473-5598 $g Roč. 31, č. 2 (2013), s. 321-332
856    41
$u https://pubmed.ncbi.nlm.nih.gov/23307303 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20131002 $b ABA008
991    __
$a 20191024110343 $b ABA008
999    __
$a ok $b bmc $g 995807 $s 830165
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2013 $b 31 $c 2 $d 321-332 $i 1473-5598 $m Journal of hypertension $n J Hypertens $x MED00002723
GRA    __
$a NT11230 $p MZ0
GRA    __
$a NT12171 $p MZ0
LZP    __
$a Pubmed-20131002

Find record

Citation metrics

Archiving options