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

Wang W, Shen J, Cui Y, Jiang J, Chen S, Peng J, Wu Q - Kidney Int. (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cardiology, Nephrology and Hypertension, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.

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.

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Metabolic studies and reduced sodium excretion in Cor−/− miceFood and water intake, urine volume (a), plasma eletrolytes (b) and urinary Na+, Cl− and K+ excretion (c) were measured in WT and Cor−/− mice on 0.3% and 4% NaCl diets. n.s., not statistically significant; *p<0.01 vs. WT on 0.3% NaCl diet; †p<0.01 vs. Cor−/− on 0.3% NaCl diet; ‡p<0.01 vs. WT on 4% NaCl diet 1 week; §p<0.05 vs. Cor−/− on 4% NaCl diet 1 week by two-way ANOVA; n=8–16 per group.
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Figure 2: Metabolic studies and reduced sodium excretion in Cor−/− miceFood and water intake, urine volume (a), plasma eletrolytes (b) and urinary Na+, Cl− and K+ excretion (c) were measured in WT and Cor−/− mice on 0.3% and 4% NaCl diets. n.s., not statistically significant; *p<0.01 vs. WT on 0.3% NaCl diet; †p<0.01 vs. Cor−/− on 0.3% NaCl diet; ‡p<0.01 vs. WT on 4% NaCl diet 1 week; §p<0.05 vs. Cor−/− on 4% NaCl diet 1 week by two-way ANOVA; n=8–16 per group.

Mentions: To understand the mechanism underlying the observed salt-sensitive hypertension in Cor−/− mice, we did metabolic studies in WT and Cor−/− mice. Similar food and water intakes were found with the normal salt diet (Figure 2a). On the high salt diet, food intakes remained unchanged, but water intakes and urine volumes increased similarly in WT and Cor−/− mice during the first week and remained at the high levels in weeks 2 and 3. Levels of plasma Na+, Cl−, and K+ were unchanged in these mice on the high-salt diet (Figure 2b). Apparently, plasma electrolyte balance was maintained by increased urinary Na+/Cl− excretion (Figure 2c). Compared to WT mice, however, Cor−/− mice had reduced Na+/Cl− excretion during the first week of high salt diet. The difference in Na+/Cl− excretion between WT and Cor−/− mice narrowed in the following weeks (Figure 2c), indicating that a steady state of salt-water balance was reached gradually in Cor−/− mice. In contrast, levels of urinary K+ excretion were similar in Cor−/− and WT mice (Figure 2c).


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

Wang W, Shen J, Cui Y, Jiang J, Chen S, Peng J, Wu Q - Kidney Int. (2012)

Metabolic studies and reduced sodium excretion in Cor−/− miceFood and water intake, urine volume (a), plasma eletrolytes (b) and urinary Na+, Cl− and K+ excretion (c) were measured in WT and Cor−/− mice on 0.3% and 4% NaCl diets. n.s., not statistically significant; *p<0.01 vs. WT on 0.3% NaCl diet; †p<0.01 vs. Cor−/− on 0.3% NaCl diet; ‡p<0.01 vs. WT on 4% NaCl diet 1 week; §p<0.05 vs. Cor−/− on 4% NaCl diet 1 week by two-way ANOVA; n=8–16 per group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3376235&req=5

Figure 2: Metabolic studies and reduced sodium excretion in Cor−/− miceFood and water intake, urine volume (a), plasma eletrolytes (b) and urinary Na+, Cl− and K+ excretion (c) were measured in WT and Cor−/− mice on 0.3% and 4% NaCl diets. n.s., not statistically significant; *p<0.01 vs. WT on 0.3% NaCl diet; †p<0.01 vs. Cor−/− on 0.3% NaCl diet; ‡p<0.01 vs. WT on 4% NaCl diet 1 week; §p<0.05 vs. Cor−/− on 4% NaCl diet 1 week by two-way ANOVA; n=8–16 per group.
Mentions: To understand the mechanism underlying the observed salt-sensitive hypertension in Cor−/− mice, we did metabolic studies in WT and Cor−/− mice. Similar food and water intakes were found with the normal salt diet (Figure 2a). On the high salt diet, food intakes remained unchanged, but water intakes and urine volumes increased similarly in WT and Cor−/− mice during the first week and remained at the high levels in weeks 2 and 3. Levels of plasma Na+, Cl−, and K+ were unchanged in these mice on the high-salt diet (Figure 2b). Apparently, plasma electrolyte balance was maintained by increased urinary Na+/Cl− excretion (Figure 2c). Compared to WT mice, however, Cor−/− mice had reduced Na+/Cl− excretion during the first week of high salt diet. The difference in Na+/Cl− excretion between WT and Cor−/− mice narrowed in the following weeks (Figure 2c), indicating that a steady state of salt-water balance was reached gradually in Cor−/− mice. In contrast, levels of urinary K+ excretion were similar in Cor−/− and WT mice (Figure 2c).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cardiology, Nephrology and Hypertension, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.

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.

Show MeSH
Related in: MedlinePlus