Hypertension in mice lacking the proatrial natriuretic peptide convertase corin

• DOI: 10.1073/pnas.0407234102
• Publication Date: 2005-01-07T03:41:26Z
• Authors: Joyce C. Y. Chan; Ole Knudson; Faye Wu; John Morser; William P. Dole; Qingyu Wu
• Keywords: Male; 0301 basic medicine; 0303 health sciences; Serine Endopeptidases; Embryonic Development; Cardiomegaly; Sodium Chloride; Pregnancy Complications; Mice; Proteinuria; 03 medical and health sciences; Pregnancy; Hypertension; Animals; Female; Protein Precursors; Atrial Natriuretic Factor

Atrial natriuretic peptide (ANP) is a cardiac hormone that regulates blood pressure. In cardiomyocytes, the hormone is synthesized as a precursor, proatrial natriuretic peptide (pro-ANP), which is proteolytically converted to active ANP. Corin is a cardiac transmembrane serine protease that has been shown to process pro-ANP in vitro , but its physiological importance had not been established. Here, we show that corin-deficient ( Cor -/- ) mice develop normally during embryogenesis and survive to postnatal life. Cor -/- mice have elevated levels of pro-ANP but no detectable levels of ANP as compared with WT littermates. Infusion of an active recombinant soluble corin transiently restores pro-ANP conversion, resulting in the release of circulating biologically active ANP. Using radiotelemetry to assess blood pressure, we find that Cor -/- mice have spontaneous hypertension as compared with WT mice, and it is enhanced after dietary salt loading. Pregnant Cor -/- mice demonstrate late-gestation proteinuria and enhanced high blood pressure during pregnancy. In addition, Cor -/- mice exhibit cardiac hypertrophy resulting in a mild decline in cardiac function later in life. Thus, our data establish corin as the physiological pro-ANP convertase and indicate that corin deficiency may contribute to hypertensive heart disease.