A genetic model provides evidence that the receptor for atrial natriureticpeptide (guanylyl cyclase-A) inhibits cardiac ventricular myocyte hypertrophy

Guanylyl cyclase-A (NPR-A; GC-A) is the major and possibly the only recepto r for atrial natriuretic peptide (ANP) or B-type natriuretic peptide. Altho ugh mice deficient in CC-A display an elevated blood pressure, the resultan t cardiac hypertrophy is much greater than in other mouse models of hyperte nsion. Here we overproduce GC-A in the cardiac myocytes of wild-type or GC- A null animals. Introduction of the GC-A transgene did not alter blood pres sure or heart rate as a function of genotype, Cardiac myocyte size was larg er (approximately 20%) in GC-A null than in wild-type animals. However, int roduction of the CC-A transgene reduced cardiac myocyte size in both wild-t ype and null mice. Coincident with the reduction in myocyte size, both ANP mRNA and ANP content were significantly reduced by overexpression of GC-A, and th is reduction was independent of genotype, This genetic model, theref ore, separates a regulation of cardiac myocyte size by blood pressure from local regulation by a CC-mediated pathway.