Inhibition of Na + -H + Exchange Prevents Hypertrophy, Fibrosis, and Heart Failure in β 1 -Adrenergic Receptor Transgenic Mice

• DOI: 10.1161/01.res.0000014966.97486.c0
• Publication Date: 2002-07-28T23:16:47Z
• Authors: Stefan Engelhardt; Lutz Hein; Ursula Keller; Kerstin Klämbt; Martin J. Lohse
• Keywords: Heart Failure; Myocardium; Blotting, Western; Body Weight; Administration, Oral; Gene Expression; Cardiomegaly; Mice, Transgenic; Organ Size; Fibrosis; Guanidines; Myocardial Contraction; Drug Administration Schedule; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; 0302 clinical medicine; Animals; Humans; RNA, Messenger; Enzyme Inhibitors; Receptors, Adrenergic, beta-1

Chronic stimulation of the beta(1)-adrenergic receptor leads to hypertrophy and heart failure in transgenic mice contributes disease progression patients. The cellular mechanisms underlying these detrimental effects are largely unknown. In this study, we have identified cardiac Na(+)-H(+) exchanger (NHE1) as a novel mediator adrenergically induced failure. beta(1)-Adrenergic showed upregulation both NHE1 mRNA (+140+/-6%) protein (+42+/-19%). order test whether increased is causally related beta(1)-adrenergic-induced hypertrophy, fibrosis, failure, (TG) wild-type (WT) littermates were treated with diet containing 6000 ppm inhibitor cariporide or control chow for 8 months. There was significant myocytes (2.3-fold increase myocyte cross-sectional area), which virtually absent cariporide-fed animals. Interstitial fibrosis prominent throughout left ventricular wall nontreated (4.8-fold collagen volume fraction); treatment completely prevented development fibrosis. Left catheterization that also loss contractile function mice: whereas untreated decrease contractility (5250+/-570 mm Hg/s TG versus 7360+/-540 WT, dp/dt(max)), by (8150+/-520 cariporide). Inhibition beta(1)-receptor mice. We conclude 1 essential chronic heart.