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. 2025 Jan 31;136(3):321-324.
doi: 10.1161/CIRCRESAHA.124.325058. Epub 2025 Jan 10.

Arterial NALCN Knockdown Ameliorates Mineralocorticoid-Induced Hypertension and Arterial Overcontractility

Hyeryeong Lee #  1 , Solah Park #  1 , Dong Jun Sung #  2 , Jin Ryeol An  1 , Mi Seon Seo  1 , Hyun Ju Noh  1 , Jueng Soo You  3 , Sung Hea Kim  4 , Hana Cho  5 , Bokyung Kim  1 , Sang Woong Park  6 , Young Min Bae  1
Affiliations

Arterial NALCN Knockdown Ameliorates Mineralocorticoid-Induced Hypertension and Arterial Overcontractility

Hyeryeong Lee et al. Circ Res. .
No abstract available

Keywords: aldosterone; hypertension; mineralocorticoids; muscle, smooth; serotonin; sodium channel; vasoconstriction.

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Conflict of interest statement

Male Sprague-Dawley rats were obtained for the experiments.

Figures

Figure.
Figure.
Upregulation of the Na+-leak channel (NALCN) by mineralocorticoids contributes to increased arterial contractility and the development of hypertension. A, Effects of low Na+ (LNa+) and nifedipine on arterial contractility. Ai and Aii, Representative traces of basal arterial tone and the effects of LNa+ (23-mmol/L Na+) and nifedipine (1 µmol/L). The LNa+ solution was prepared by equimolar substitution of Na+ with N-methyl-D-glucamine+ in the bathing solution. Aiii, Summary of Ai and Aii. Aiv through Avii, Representative responses of mesenteric arteries to cumulative concentrations of 5-hydroxytryptamine (5-HT) under normal and LNa+ conditions. Aviii, Summary of Aiv through Avii. Aix, Effects of benzamil (epithelial Na+ channel [ENaC] blocker) on the 5-HT-induced vasoconstrictions. B, Nonrenal influences of aldosterone on arterial contractility and NALCN expression (ex vivo study). The aorta and mesenteric arterial rings were incubated for 2 days in a conventional incubator under various conditions. Bi through Biv, Representative traces showing basal tone and 5-HT-induced mesenteric arterial constrictions. Bv, Summary of ex vivo effects of aldosterone on 5-HT-induced mesenteric arterial constrictions and the effects of NALCN knockdown (K/D). Bvi, Western blotting experiment showing NALCN protein levels under each condition (in the aorta). Upper, Representative blotting. Lower, Summarized results. C, Transient NALCN K/D ameliorates both hypertension and increased arterial contractility. Ci, Schematic of the experimental protocol. Cii, Systolic blood pressure (SBP) measurements over time. Ciii, NALCN protein levels in the mesenteric arteries, brains, aorta, and kidneys from sham, deoxycorticosterone acetate-salt hypertension (DOCASH), and NALCN K/D DOCASH rats. Civ and Cv, Representative traces of mesenteric arterial contractile responses from DOCASH and NALCN K/D DOCASH rats. Cvi, Comparison of concentration-dependent arterial constrictions by 5-HT between DOCASH and NALCN K/D DOCASH under normal and LNa+ conditions. We used biological replicates in this study, with n representing the number of rats used. For data sets with n>10, normality was assessed using the Shapiro-Wilk test. Statistical analyses were conducted as follows: Aiii, Aix, and Ciii (aorta, kidney) were analyzed using the Mann-Whitney U test, while Aviii, Bv, Bvi, and Ciii were analyzed using the Kruskal-Wallis test with Holm-Bonferroni correction. Cii was analyzed using the Friedman test to evaluate time-dependent blood pressure changes within groups, the Wilcoxon signed-rank test to compare each time point (14, 21, 28, and 32 days) with the 7-day point within specific groups, and the Mann-Whitney U test was used to compare blood pressure differences between groups after siRNA injection. Notably, corrected P values were not applied to the analysis of Cii. Statistical significance is indicated as * or # or @ for P<0.05 and **, ##, or @@ for P<0.01.
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References

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