Hypertension in mice lacking the proatrial natriuretic peptide convertase corin.
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.
Chan
Joyce C Y
JC
Berlex Biosciences, Richmond, CA 94804, USA. joycecy_chan@yahoo.com
Knudson
Ole
O
Wu
Faye
F
Morser
John
J
Dole
William P
WP
Wu
Qingyu
Q
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000378:metabolism*; D006332:Cardiomegaly / Q000209:etiology; D047108:Embryonic Development; D005260:Female; D006973:Hypertension / Q000209:etiology*; D008297:Male; D051379:Mice; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology; D011498:Protein Precursors / Q000378:metabolism; D011507:Proteinuria / Q000209:etiology; D012697:Serine Endopeptidases / Q000172:deficiency* / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology
D011498:Protein Precursors; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; C485617:Corin protein, mouse; D012697:Serine Endopeptidases