Impaired sodium excretion and salt-sensitive hypertension in corin-deficient mice

Abstract

Corin is a protease that activates atrial natriuretic peptide, a cardiac hormone important in the control of blood pressure and salt-water balance. Here we examined the role of corin in regulating blood pressure and sodium homeostasis upon dietary salt challenge. Radiotelemetry-tracked blood pressure in corin knockout mice on a high salt diet (4% sodium chloride) was significantly increased; however, there was no such change in similarly treated wild type mice. In the knockout mice on the high salt diet there was an impairment of urinary sodium excretion and an increase in body weight, but no elevation of plasma renin or serum aldosterone levels. When the knockout mice on the high salt diet were treated with amiloride, an epithelial sodium channel blocker that inhibits renal sodium reabsorption, the impaired urinary sodium excretion and increased body weight were normalized. Amiloride treatment also reduced high blood pressure caused by the high salt diet in these mice. Thus, the lack of corin in mice impairs their adaptive renal response to high dietary salt, suggesting that corin deficiency may represent an important mechanism underlying salt-sensitive hypertension.

Epithelial Sodium Transport and Its Control by Aldosterone: The Story of Our Internal Environment Revisited

“…This is a rather unusual situation described for only few genes: uromodulin (247,273,322) with a common noncoding variant within the GRE of the promotor and corin (76,272,(335)(336)(337)346) with a SNP in a coding region of the frizzle domain (R539C) found in 12% of African-Americans with hypertension. Common variants of APOL1 that confer resistance to trypanosomal infections in many regions of Africa are linked to the developpment of CKD (thus indirectly to hypertension) in African-American populations (250,340).…”

Atrial natriuretic peptide in cardiovascular biology and disease (NPPA)

“…ANP. In mice, disrupting the Corin gene abolished pro-ANP processing and caused spontaneous hypertension (Chan et al, 2005; Wang et al, 2012b), indicating that corin is the primary pro-ANP convertase in vivo . In humans, CORIN variants and mutations that impair corin activity have been identified in patients with hypertension and heart disease (Dong et al, 2013; Dries et al, 2005; Wang et al, 2012a; Wang et al, 2008; Zhang et al, 2014).…”

Increased Dietary Salt Intake Does Not Influence Influenza A Virus–Induced Disease Severity in Mice

“…The three salt diets, despite having 10-fold increments of sodium, did not lead to any changes in serum sodium levels. An earlier study (21) using similar salt diets (0.3% NaCl and 4% NaCl) in mice also found that serum Na + , Cl − , and K + levels were unchanged in the two groups of mice. In the same study, Wang et al .…”