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(Hypertension. 2008;51:540.)
© 2008 American Heart Association, Inc.

Original Articles Part 2

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

Robert Fischer; Ralf Dechend; Fatimunnisa Qadri; Marija Markovic; Sandra Feldt; Florian Herse; Joon-Keun Park; Andrej Gapelyuk; Ines Schwarz; Udo B. Zacharzowsky; Ralph Plehm; Erdal Safak; Arnd Heuser; Alexander Schirdewan; Friedrich C. Luft; Wolf-Hagen Schunck; Dominik N. Muller

From the Medical Faculty of the Charité (R.F., R.D., S.F., F.H., A.G., I.S., U.B.Z., E.S., A.S., F.C.L., D.N.M.), Experimental and Clinical Research Center, Franz Volhard Clinic and HELIOS Klinikum Berlin-Buch, Berlin, Germany; Max-Delbrueck-Center for Molecular Medicine (F.Q., M.M., R.P., A.H., F.C.L., W-H.S., D.N.M.), Berlin-Buch, Germany; Medical School of Hannover (J-K.P.), Hannover, Germany.

Correspondence to Robert Fischer, Experimental and Clinical Research Center, Max-Delbrueck-Center, Lindenberger Weg 80, 13125 Berlin, Germany. E-mail robert.fischer{at}charite.de

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 QT_c 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.

Key Words: angiotensin II • renin inhibition • n-3 PUFA • arrhythmias • magnetocardiography