Fachbereich Veterinärmedizin



    Dietary n-3 Polyunsaturated Fatty Acids and Direct Renin Inhibition Improve Electrical Remodeling in a Model of High Human Renin Hypertension (2008)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Fischer, R.
    Dechend, R.
    Qadri, F.
    Markovic, M.
    Feldt, S.
    Herse, F.
    Park, J-K
    Gapelyuk, A.
    Schwarz, I.
    Zacharzowsky, U. B.
    Plehm, R.
    Safak, E.
    Heuser, A.
    Schirdewan, A.
    Luft, F. C.
    Schunck, W-H
    Muller, D. N.
    Hypertension; 51(2) — S. 540–546
    ISSN: 0194-911x
    URL (Volltext): http://hyper.ahajournals.org/cgi/reprint/51/2/540
    Pubmed: 18158339
    Institut für Veterinär-Physiologie

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    14163 Berlin
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    Abstract / Zusammenfassung

    We compared the effect n-3 polyunsaturated fatty acids (PUFAs) with direct renin inhibition on electrophysiological remodeling in angiotensin II?induced cardiac injury. We treated double-transgenic rats expressing the human renin and angiotensinogen genes (dTGRs) from week 4 to 7 with n-3 PUFA ethyl-esters (Omacor; 25-g/kg diet) or a direct renin inhibitor (aliskiren; 3 mg/kg per day). Sprague-Dawley rats were controls. We performed electrocardiographic, magnetocardiographic, and programmed electrical stimulation. Dietary n-3 PUFAs increased the cardiac content of eicosapentaenoic and docosahexaenoic acid. At week 7, mortality in dTGRs was 31%, whereas none of the n-3 PUFA- or aliskiren-treated dTGRs died. Systolic blood pressure was modestly reduced in n-3 PUFA-treated (180±3 mm Hg) compared with dTGRs (208±5 mm Hg). Aliskiren-treated dTGRs and Sprague-Dawley rats were normotensive (110±3 and 119±6 mm Hg, respectively). Both n-3 PUFA?treated and untreated dTGRs showed cardiac hypertrophy and increased atrial natriuretic peptide levels. Prolonged QRS and QTc intervals and increased T-wave dispersion in dTGRs were reduced by n-3 PUFAs or aliskiren. Both treatments reduced arrhythmia induction from 75% in dTGRs to 17% versus 0% in Sprague-Dawley rats. Macrophage infiltration and fibrosis were reduced by n-3 PUFAs and aliskiren. Connexin 43, a mediator of intermyocyte conduction, was redistributed to the lateral cell membranes in dTGRs. n-3 PUFAs and aliskiren restored normal localization to the intercalated disks. Thus, n-3 PUFAs and aliskiren improved electrical remodeling, arrhythmia induction, and connexin 43 expression, despite a 70-mm Hg difference in blood pressure and the development of cardiac hypertrophy.