Altered expression of natriuretic peptide receptors in proANP gene disrupted mice

Background: The atrial natriuretic peptide (ANP) family is a complex system consisting of at least three polypeptides and at least three types of rece ptor. Each peptide interacts with different types of receptor at varying de grees of affinity. To determine if natriuretic peptide levels influence nat riuretic peptide receptor expression and regulation, we examined the expres sion of guanylyl cyclase linked GC-A, GC-B and C-receptor in the lungs of m ice 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 ribonucleas e 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 mut ant ANP-/- mice. In addition, C-receptor mRNA level in ANP+/- and ANP-/- wa s significantly lower than ANPS+/+ mice. The C-receptor results were confir med by receptor binding assays and affinity cross-linking studies. Conclusi ons: Taken together these data suggest that permanent removal of ANP from t he 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 ge ne disrupted mice. We postulated that changes in the natriuretic peptide re ceptor population may result in chronic hypertension and cardiac hypertroph y in the ANP-/- mice. (C) 2000 Elsevier Science B.V. All rights reserved.