Development of the heart in ANP−/− mice during early postnatal period

Abstract

Disruption of the proANP gene results in marked cardiac hypertrophy, chronic and salt‐sensitive hypertension. It is unclear when cardiac hypertrophy in ANP−/− mice appears during development. The present study was designed to examine cardiac hypertrophy in ANP−/− mice during early postnatal development and correlate it with expression of the renin‐angiotensin (RAS) and the extracellular matrix (ECM) systems. Hearts were excised from 1–5 week old neonatal and 12 week adult male ANP+/+ and ANP−/− mice. Total mRNA was extracted from whole neonatal hearts and adult left ventricles, and evaluated using Northern blot analysis and quantitative RT‐PCR. Cardiac hypertrophy as indicated by an increase in heart/body weight ratio was evident in ANP−/− mice at all age groups. The most significant molecular changes were an increase in the expression of cardiac BNP mRNA level and a decrease in metalloproteinase 2 (MMP‐2) mRNA of ANP−/− as compared to the ANP+/+ mice. These data support the idea that the renin‐angiotensin system plays a minor role in the development of cardiac hypertrophy in the proANP gene disrupted mice and suggest the essential role of ANP and ECM in the development and maintenance of cardiac hypertrophy in the ANP−/− mice. Supported by the Heart and Stroke Foundation of Ontario.