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1 Laboratory for Molecular Cardiology, Rigshospitalet, Copenhagen, Denmark
2 Department of Medicine B, Rigshospitalet , The Laboratory of Molecular and Cellular Cardiology, Copenhagen, Denmark
3 Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark
4 Department of Virology and Molecular Toxicology, Novo Nordisk A/S, Maalov, Denmark
5 Department of Clinical Chemistry, Rigshospitalet, Copenhagen, Denmark
* To whom correspondence should be addressed. E-mail: tue{at}rh.dk.
Both atrial and brain natriuretic peptide affects development of cardiac hypertrophy and fibrosis via binding to the natriuretic peptide receptor A (NPR-A) in the heart. A putative clearance receptor NPR-C is believed to regulate cardiac levels of atrial and brain natriuretic peptide. The renin-angiotensin system also affects cardiac hypertrophy and fibrosis. In this study we examined the expression of genes for the natriuretic peptide receptors in rats with pressure-overload cardiac hypertrophy. The angiotensin II type 1 receptor was blocked with losartan (10 mg/kg/day) to investigate a possible role of the renin-angiotensin system in regulation of natriuretic peptide and NPR gene expression. The ascending aorta was banded in 84 rats during hypdorm/isoflurane anesthesia; after 4 weeks the rats were randomized to treatment with losartan or placebo. The left ventricle of the heart was removed 1, 2, or 4 weeks later. Aortic banding increased left ventricular expression of NPR-A and NPR-C mRNA by 110% (P<0.001) and 520% (P<0.01) after 8 weeks, respectively; as expected, it also increased the expression of ANP and BNP mRNAs. Losartan induced a slight reduction of the left ventricular weight, but did not affect the expression of mRNAs for the natriuretic peptides or their receptors. Although increased gene expression not necessarily conveys a higher concentration of the protein, the data suggest that pressure-overload is accompanied by upregulation of not only ANP and BNP, but also their receptors NPR-A and NPR-C in the left ventricle.
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