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This Article Full Text Full Text (PDF) All Versions of this Article: 290/4/H1635    most recent 00612.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Christoffersen, T. E. H. Articles by Nielsen, L. B. Search for Related Content PubMed PubMed Citation Articles by Christoffersen, T. E. H. Articles by Nielsen, L. B.

Increased natriuretic peptide receptor A and C gene expression in rats with pressure-overload cardiac hypertrophy

¹Laboratory of Molecular Cardiology, ²Department of Clinical Biochemistry, and ³Laboratory of Molecular and Cellular Cardiology, Department of Medicine B, Rigshospitalet, Copenhagen; ⁴Department of Virology and Molecular Toxicology, Novo Nordisk A/S, Maalov; and ⁵Department of Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark

Submitted 8 June 2005 ; accepted in final form 28 October 2005

Both atrial (ANP) and brain (BNP) natriuretic peptide affect development of cardiac hypertrophy and fibrosis via binding to natriuretic peptide receptor (NPR)-A in the heart. A putative clearance receptor, NPR-C, is believed to regulate cardiac levels of ANP and BNP. The renin-angiotensin system also affects cardiac hypertrophy and fibrosis. In this study we examined the expression of genes for the NPRs in rats with pressure-overload cardiac hypertrophy. The ANG II type 1 receptor was blocked with losartan (10 mg·kg^–1·day^–1) 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 Hypnorm/Dormicum-isoflurane anesthesia; after 4 wk the rats were randomized to treatment with losartan or placebo. The left ventricle of the heart was removed 1, 2, or 4 wk later. Aortic banding increased left ventricular expression of NPR-A and NPR-C mRNA by 110% (P < 0.001) and 520% (P < 0.01), respectively, after 8 wk; as expected, it also increased the expression of ANP and BNP mRNAs. Losartan induced a slight reduction of left ventricular weight but did not affect the expression of mRNAs for the natriuretic peptides or their receptors. Although increased gene expression does not necessarily convey 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.

losartan; angiotensin II type 1 receptor; renin

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