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Effects of transgenic expression of dopamine beta hydroxylase (Dbh) gene on blood pressure in spontaneously hypertensive rats
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SYSNO ASEP 0467648 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Effects of transgenic expression of dopamine beta hydroxylase (Dbh) gene on blood pressure in spontaneously hypertensive rats Author(s) Pravenec, Michal (FGU-C) RID, ORCID
Landa, Vladimír (FGU-C) RID
Zídek, Václav (FGU-C) RID
Mlejnek, Petr (FGU-C) RID, ORCID
Šilhavý, Jan (FGU-C) RID, ORCID
Mir, S.A. (US)
Vaingankar, S. M. (US)
Wang, J. (US)
Kurtz, T. W. (US)Source Title Physiological Research. - : Fyziologický ústav AV ČR, v. v. i. - ISSN 0862-8408
Roč. 65, č. 6 (2016), s. 1039-1044Number of pages 6 s. Language eng - English Country CZ - Czech Republic Keywords spontaneously hypertensive rat ; transgenic ; dopamine beta hydroxylase ; catecholamines ; blood pressure ; left ventricular mass Subject RIV FB - Endocrinology, Diabetology, Metabolism, Nutrition R&D Projects GAP301/12/0696 GA ČR - Czech Science Foundation (CSF) TA02010013 GA TA ČR - Technology Agency of the Czech Republic (TA ČR) Institutional support FGU-C - RVO:67985823 UT WOS 000391198200015 EID SCOPUS 85011844896 Annotation The spontaneously hypertensive rat (SHR) is the most widely used animal model of essential hypertension and left ventricular hypertrophy. Catecholamines play an important role in the pathogenesis of both essential hypertension in humans and in the SHR. Recently, we obtained evidence that the SHR harbors a variant in the gene for dopamine beta hydroxylase (Dbh) that is associated with reduced adrenal expression of Dbh mRNA and reduced DBH enzymatic activity which correlated negatively with blood pressure. In the current study, we used a transgenic experiment to test the hypothesis that reduced Dbh expression predisposes the SHR to hypertension and that augmentation of Dbh expression would reduce blood pressure. We derived 2 new transgenic SHR-Dbh lines expressing Dbh cDNA under control of the Brown Norway (BN) wild type promoter. We found modestly increased adrenal expression of Dbh in transgenic rats versus SHR non-transgenic controls that was associated with reduced adrenal levels of dopamine and increased plasma levels of norepinephrine and epinephrine. The observed changes in catecholamine metabolism were associated with increased blood pressure and left ventricular mass in both transgenic lines. We did not observe any consistent changes in brainstem levels of catecholamines or of mRNA levels of Dbh in the transgenic strains. Contrary to our initial expections, these findings are consistent with the possibility that genetically determined decreases in adrenal expression and activity of DBH do not represent primary determinants of increased blood pressure in the SHR model. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2017
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