title: 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.
authors.affiliation: Department of Molecular Cardiology, Nephrology and Hypertension, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Shen
authors.forename: Yujie
authors.initials: Y
authors.lastname: Cui
authors.forename: Jingjing
authors.initials: J
authors.lastname: Jiang
authors.forename: Shenghan
authors.initials: S
authors.lastname: Chen
authors.forename: Jianhao
authors.initials: J
authors.lastname: Peng
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Wu
mesh_terms: D000450:Aldosterone / Q000097:blood; D000584:Amiloride / Q000494:pharmacology; D017311:Amlodipine / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory / Q000379:methods; D001835:Body Weight; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009318:Natriuresis / Q000187:drug effects; D012083:Renin / Q000097:blood; D012697:Serine Endopeptidases / Q000172:deficiency* / Q000235:genetics; D026941:Sodium Channel Blockers / Q000494:pharmacology; D017673:Sodium Chloride, Dietary; D013686:Telemetry; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D015415:Biomarkers; D002121:Calcium Channel Blockers; D026941:Sodium Channel Blockers; D017673:Sodium Chloride, Dietary; D017311:Amlodipine; D000450:Aldosterone; D000584:Amiloride; C485617:Corin protein, mouse; D012697:Serine Endopeptidases; D012083:Renin; D019808:Losartan