Increased natriuretic peptide receptor A and C gene expression in rats with pressure-overload cardiac hypertrophy.
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.
Christoffersen
Tue E H
TE
Laboratory of Molecular Cardiology, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. tue@rh.dk
Aplin
Mark
M
Strom
Claes C
CC
Sheikh
Soren P
SP
Skott
Ole
O
Busk
Peter K
PK
Haunso
Stig
S
Nielsen
Lars B
LB
D000818:Animals; D005786:Gene Expression Regulation; D006162:Guanylate Cyclase / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D012084:Renin-Angiotensin System
D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; C073616:atrial natriuretic factor receptor C