Ventricular expression of natriuretic peptides in Npr1-/- mice with cardiac hypertrophy and fibrosis

1 Department of Medicine, Christchurch School of Medicine, Christchurch, New Zealand; and 2 Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7525 Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones that regulate blood pressure and volume, and exert their biological actions via the natriuretic peptide receptor-A gene ( Npr1 ). Mice lacking Npr1 ( Npr / ) have marked cardiac hypertrophy and fibrosis disproportionate to their increased blood pressure. This study examined the relationships between ANP and BNP gene expression, immunoreactivity and fibrosis in cardiac tissue, circulating ANP levels, and ANP and BNP mRNA during embryogenesis in Npr1 / mice. Disruption of the Npr1 signaling pathway resulted in augmented ANP and BNP gene and ANP protein expression in the cardiac ventricles, most pronounced for ANP mRNA in females [414 ± 57 in Npr1 / ng/mg and 124 ± 25 ng/mg in wild-type (WT) by Taqman assay, P