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

Abstract

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.

• Authors: Tue E H Christoffersen, Mark Aplin, Claes C Strom, Soren P Sheikh, Ole Skott, Peter K Busk, Stig Haunso, Lars B Nielsen
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 290 Issue 4 Pg. H1635-41 (Apr 2006) ISSN: 0363-6135 [Print] United States
• PMID: 16272201 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Guanylate Cyclase
• Receptors, Atrial Natriuretic Factor
• atrial natriuretic factor receptor A
• atrial natriuretic factor receptor C

Topics

• Animals
• Gene Expression Regulation
• Guanylate Cyclase (metabolism)
• Heart Ventricles (metabolism)
• Hypertrophy, Left Ventricular (metabolism)
• Male
• Rats
• Rats, Wistar
• Receptors, Atrial Natriuretic Factor (metabolism)
• Renin-Angiotensin System