© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Altered expression of natriuretic peptide receptors in proANP gene disrupted mice
aDepartment of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6
bDepartment of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada K7L 3N6
cDepartment of Physiology, University of Texas Health Sciences Center, San Antonio, TX, USA
dThe Howard Hughes Medical Institute, The Jackson Laboratory, Bar Harbor, Maine, and Department of Ophthalmology, Tafts University School of Medicine, Boston, MA, USA
* Corresponding author. Tel.: +1-613-533-2600; fax: +1-613-533-2566 pangsc{at}post.queensu.ca
Background: The atrial natriuretic peptide (ANP) family is a complex system consisting of at least three polypeptides and at least three types of receptor. Each peptide interacts with different types of receptor at varying degrees of affinity. To determine if natriuretic peptide levels influence natriuretic peptide receptor expression and regulation, we examined the expression of guanylyl cyclase linked GC-A, GC-B and C-receptor in the lungs of mice with a mutation that inactivates the ANP gene (Nppa). Methods: The mRNA level of GC-A, GC-B and C-receptor in the lung were studied by ribonuclease protection assays (RPA). Results: Results of RPA showed that although the mRNA level of GC-A and GC-B of heterozygous ANP+/– was not different from wild type ANP+/+ mice, they were significantly higher in the homozygous mutant ANP–/– mice. In addition, C-receptor mRNA level in ANP+/– and ANP–/– was significantly lower than ANP+/+ mice. The C-receptor results were confirmed by receptor binding assays and affinity cross-linking studies. Conclusions: Taken together these data suggest that permanent removal of ANP from the natriuretic peptide system results in an up-regulation of GC-A and GC-B, and a corresponding down-regulation of C-receptor in the lung of proANP gene disrupted mice. We postulated that changes in the natriuretic peptide receptor population may result in chronic hypertension and cardiac hypertrophy in the ANP–/– mice.
KEYWORDS Gene expression; Hypertension; Hypertrophy; Natriuretic peptide; Receptors
1 NV and MYT made equal contributions in this investigation.
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