Open AccessLeft But Not Right Cardiac Hypertrophy in Atrial Natriuretic Peptide Receptor–Deficient Mice Is Prevented by Angiotensin Type 1 Receptor Antagonist Losartan
Author(s) -
Rita Holtwick,
Hideo A. Baba,
Elisabeth Ehler,
Dorothée Risse,
Melanie Vobeta,
Joseph Gehrmann,
Melanie Pierkes,
Michaela Kühn
Publication year - 2002
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-200211000-00010
Subject(s) - losartan , medicine , atrial natriuretic peptide , endocrinology , angiotensin ii , angiotensin ii receptor type 1 , renin–angiotensin system , natriuretic peptide , left ventricular hypertrophy , muscle hypertrophy , endothelin receptor , right ventricular hypertrophy , brain natriuretic peptide , angiotensin ii receptor antagonist , angiotensin receptor , receptor antagonist , pulmonary hypertension , receptor , antagonist , heart failure , blood pressure
Mice with a genetic deletion of the atrial natriuretic peptide (ANP) receptor, guanylyl cyclase A (GC-A -/-), have chronic arterial hypertension and cardiac hypertrophy from the first day of life. To characterize the role of the angiotensin II and endothelin systems in the development of this cardiovascular phenotype, the effects of chronic treatment with either the angiotensin type I (AT1) receptor antagonist losartan or the endothelin A receptor antagonist BSF208075 were tested. Losartan almost completely reversed systemic arterial hypertension and left ventricular hypertrophy of GC-A -/- mice. This was accompanied by a marked regression of the left ventricular mRNA expression of cardiac hypertrophy markers such as ANP and brain natriuretic peptide and a significant reduction of left ventricular and pulmonary interstitial collagen accumulation. BSF208075 had no effect on any of these cardiovascular parameters. Intriguingly, GC-A -/- mice also showed a very marked right ventricular hypertrophy, which was not reversed by losartan or BSF208075 treatment. Analyses of components of the renin-angiotensin system (RAS) revealed an inhibition of renal and systemic RAS contrasting with increased local left ventricular angiotensin II levels in GC-A -/- mice. Collectively, the results suggest that RAS plays a more important role than the endothelin system in the pathogenesis of arterial hypertension as well as left ventricular hypertrophy and fibrosis in GC-A gene-disrupted mice.