Epithelial Sodium Channel (ENaC) in Endothelium Modulates Vascular Reactivity with a High Salt Diet

Aldosterone is thought to be the main hormone to stimulate the epithelial sodium channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) comprising the late distal convoluted tubule (DCT2), the connecting tubule (CNT) and the entire collecting duct (CD). There is immunohistochemical evidence for an axial gradient of ENaC expression along the ASDN with highest expression in the DCT2 and CNT. However, most of our knowledge about renal ENaC function stems from studies in the cortical collecting duct (CCD). Here we investigated ENaC function in the transition zone of DCT2/CNT or CNT/CCD microdissected from mice maintained on different sodium diets to vary plasma aldosterone levels. Single-channel recordings demonstrated amiloride-sensitive Na+ channels in DCT2/CNT with biophysical properties typical for ENaC previously described in CNT/CCD. In animals maintained on a standard salt diet, the average ENaC-mediated whole cell current (Δ Iami) was higher in DCT2/CNT than in CNT/CCD. A low salt diet increased Δ Iami in CNT/CCD but had little effect on Δ Iami in DCT2/CNT. To investigate whether aldosterone is necessary for ENaC activity in the DCT2/CNT, we used aldosterone synthase knockout (AS−/−) mice that lack aldosterone. In CNT/CCD of AS−/− mice, Δ Iami was lower than that in wild-type (WT) animals and was not stimulated by a low salt diet. In contrast, in DCT2/CNT of AS−/− mice, Δ Iami was similar to that in DCT2/CNT of WT animals both on a standard and on a low salt diet. We conclude that ENaC function in the DCT2/CNT is largely independent of aldosterone which is in contrast to its known aldosterone sensitivity in CNT/CCD.

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l-arginine Supplementation Increased Only Endothelium-Dependent Relaxation in Sprague-Dawley Rats Fed a High-Salt Diet by Enhancing Abdominal Aorta Endothelial Nitric Oxide Synthase Gene Expression

Clinical Medicine Insights Cardiology ◽

10.1177/1179546820902843 ◽

2020 ◽

Vol 14 ◽

pp. 117954682090284

Author(s):

Abdullahi Adejare ◽

Ahmed Oloyo ◽

Chikodi Anigbogu ◽

Smith Jaja

Keyword(s):

Gene Expression ◽

Vascular Reactivity ◽

High Salt ◽

Enos Gene ◽

Sprague Dawley ◽

High Salt Diet ◽

Salt Diet ◽

Sprague Dawley Rats ◽

Endothelium Dependent Relaxation ◽

Arginine Supplementation

Background: Abnormal vascular reactivity and reduced expression of endothelial nitric oxide synthase ( eNOS) gene are hallmark of salt-induced hypertension in rats. Although l-arginine is an established vasodilator, the mechanism by which it modulates vascular reactivity in salt-induced hypertension is not clearly understood. Objectives: This study was designed to investigate the mechanism by which oral l-arginine supplementation modulates vascular reactivity and eNOS gene expression in Sprague-Dawley rats fed a high-salt diet. Methods: Forty-eight weaned male Sprague-Dawley rats of weight range 90 to 110 g were randomly divided into 6 groups of 8 rats per group. Group I was fed normal rat chow ad libitum and served as the Normal Diet group. Group II was fed a diet that contained 8% NaCl. Groups III and IV took normal and high-salt diet, respectively, and then received oral l-arginine supplementation (100 mg/kg/day), while groups V and VI took normal and high-salt diet, respectively, and then were co-administered with both l-arginine and l-nitro-arginine methyl ester (L-NAME; 100 mg/kg/day and 40 mg/kg/day, respectively) orally. At the end of 12-week experimental period, the animals were sacrificed to assess vascular reactivity and gene expression level. Results: Our results show that high-salt diet significantly reduced ( P < .05) endothelium-dependent relaxation response to acetylcholine and qualitatively reduced eNOS gene expression in the abdominal aorta of the rats. However, l-arginine supplementation improved the impaired endothelium-dependent relaxation and nitric oxide level while ameliorating the reduced eNOS gene expressions. Conclusion: This study suggests that oral supplementation of l-arginine enhances endothelial-dependent relaxation in rats fed a high-salt diet by ameliorating eNOS gene expression in the abdominal aorta of the rats.

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Effects of Testosterone on Vascular Reactivity in Male Sprague – Dawley Rats Fed a High Salt Diet

The FASEB Journal ◽

10.1096/fasebj.26.1_supplement.872.27 ◽

2012 ◽

Vol 26 (S1) ◽

Author(s):

Ahmed Kolade Oloyo ◽

Yakubu Momoh ◽

Olusoga Sofola ◽

Adebayo Oyekan

Keyword(s):

Vascular Reactivity ◽

High Salt ◽

Sprague Dawley ◽

High Salt Diet ◽

Salt Diet ◽

Sprague Dawley Rats

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High-Salt Diet Enhances Vascular Reactivity in Pregnant Rats With Normal and Reduced Uterine Perfusion Pressure

Hypertension ◽

10.1161/01.hyp.38.3.730 ◽

2001 ◽

Vol 38 (3) ◽

pp. 730-735 ◽

Cited By ~ 26

Author(s):

Laura A. Barron ◽

Jena B. Giardina ◽

Joey P. Granger ◽

Raouf A. Khalil

Keyword(s):

Vascular Reactivity ◽

Perfusion Pressure ◽

High Salt ◽

Pregnant Rats ◽

High Salt Diet ◽

Salt Diet ◽

Uterine Perfusion

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Salt-Sensitive Hypertension of the Renal Tubular Cell–Specific NFAT5 (Nuclear Factor of Activated T-Cells 5) Knockout Mice

Hypertension ◽

10.1161/hypertensionaha.121.17435 ◽

2021 ◽

Author(s):

Akiko Hiramatsu ◽

Yuichiro Izumi ◽

Koji Eguchi ◽

Naomi Matsuo ◽

Qinyuan Deng ◽

...

Keyword(s):

Sodium Channel ◽

Epithelial Sodium Channel ◽

Urinary Sodium Excretion ◽

High Salt ◽

Sodium Reabsorption ◽

Renal Tubular Cell ◽

Activated T Cells ◽

High Salt Diet ◽

Renal Tubular ◽

Salt Sensitive Hypertension

The kidney plays a crucial role in blood pressure (BP) regulation by controlling sodium reabsorption along the nephron. NFAT5 (nuclear factor of activated T-cells 5) is a transcription factor that is expressed in various tissues including the kidney and is activated at hypertonic conditions as observed in the renal medulla; the role for kidney NFAT5 in BP regulation, however, remains still obscure. In the present study, we generated inducible and renal tubular cell–specific NFAT5 knockout (KO) mice and characterized their phenotype. The NFAT5 KO mice exhibited high BP, hypernatremia, polyuria, and low urinary sodium excretion without significant alterations in the plasma renin activity or aldosterone concentration. The mice fed a high-salt diet further increased BP, revealing salt-sensitive hypertension. The KO mice ehibited the increased gene expression of the epithelial sodium channel. Protein expression of epithelial sodium channel in the membrane fraction was also significantly increased in KO mice than in wild-type mice. Treatment with amiloride, an epithelial sodium channel blocker, corrected high BP, hypernatremia, and decreased urinary sodium excretion in KO mice to the same levels of those in wild-type mice. Finally, the effects of high-salt diet and amiloride in KO mice were confirmed by the radiotelemetry method. In conclusion, these data indicate that renal tubular NFAT5 should play an important role in regulating sodium reabsorption through epithelial sodium channel under high-salt conditions, thereby preventing salt-dependent hypertension.

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