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      Effects of high‐sodium intake on systemic blood pressure and vascular responses in spontaneously diabetic WBN/Kob‐ Lepr fa/fa rats

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          The prevalence of type 2 diabetes mellitus (T2 DM) and hypertension has markedly increased worldwide. The purpose of the present study was to examine the effects of a high‐salt intake on the systolic blood pressure ( SBP) and vascular responses in WBN/Kob‐ Lepr fa/fa ( WBKDF) rats, a new spontaneous animal model of T2 DM. Male WBKDF rats and age‐matched Wistar rats at 6 weeks of age were each divided into two groups and fed either a normal‐sodium ( NS, 0.26%) diet or high‐sodium ( HS, 8%) diet for 14 weeks: (i) Wistar rats on NS diet (Wistar‐ NS); (ii) Wistar rats on HS diet (Wistar‐ HS); (iii) WBKDF rats on NS diet ( WBKDFNS); (iv) WBKDF rats on HS diets ( WBKDFHS). Neither WBKDFNS nor Wistar‐ NS rats showed significant changes in SBP throughout the experiment, but both WBKDFHS and Wistar‐ HS exhibited significant elevation of SBP, which was more prominent ( P<.01) in WBKDFHS than in Wistar‐ HS. Phenylephrine‐induced contractions of isolated thoracic aortic rings were significantly ( P<.01) enhanced in WBKDFHS and Wistar‐ HS compared with the respective strain of rats on the NS diet. In contrast, acetylcholine‐ and nitroprusside‐induced relaxation were significantly ( P<.01) diminished in both WBKDFHS and Wistar‐ HS, and these HS diet‐induced changes were more profound ( P<.01) in WBKDF rats than in Wistar rats. Significantly ( P<.05) higher plasma concentrations of 8‐iso‐prostaglandin F and sodium ions were observed in WBKDFHS than in Wistar‐ HS. The current study demonstrated that WBKDFHS rats developed salt‐sensitive hypertension associated with vascular dysfunction. The WBKDF rat may be a useful model for investigating the etiology of hypertension with T2 DM.

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          Plasma sodium stiffens vascular endothelium and reduces nitric oxide release.

          Dietary salt plays a major role in the regulation of blood pressure, and the mineralocorticoid hormone aldosterone controls salt homeostasis and extracellular volume. Recent observations suggest that a small increase in plasma sodium concentration may contribute to the pressor response of dietary salt. Because endothelial cells are (i) sensitive to aldosterone, (ii) in physical contact with plasma sodium, and (iii) crucial regulators of vascular tone, we tested whether acute changes in plasma sodium concentration, within the physiological range, can alter the physical properties of endothelial cells. The tip of an atomic force microscope was used as a nanosensor to measure stiffness of living endothelial cells incubated for 3 days in a culture medium containing aldosterone at a physiological concentration (0.45 nM). Endothelial cell stiffness was unaffected by acute changes in sodium concentration <135 mM but rose steeply between 135 and 145 mM. The increase in stiffness occurred within minutes. Lack of aldosterone in the culture medium or treatment with the epithelial sodium channel inhibitor amiloride prevented this response. Nitric oxide formation was found down-regulated in cells cultured in aldosterone-containing high sodium medium. The results suggest that changes in plasma sodium concentration per se may affect endothelial function and thus control vascular tone.
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            The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension.

            Nineteen patients with hypertension in whom all known causes of blood pressure elevation had been ruled out were classified as "salt-sensitive" or "nonsalt-sensitive" from the changes in blood pressure with changes in sodium intake from 9 meq to 249 meq/day. With the diet containing 249 meq sodium per day, there were no statistically significant differences in plasma sodium, potassium, chloride, aldosterone, cortisol or renin activity, or in urinary potassium, aldosterone or 17-hydroxycorticosteroids between the two groups. The "salt-sensitive" patients retained more sodium on the high-sodium diet than did the patients who were not sensitive to salt ("nonsalt-sensitive"); accordingly, sodium induced more weight gain in the salt-sensitive patients.
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              Endothelial function in hypertension: the role of superoxide anion.

              Much attention has been focused on the role of nitric oxide in hypertension and cardiovascular disease. More recently, the role of superoxide anion and its interaction with nitric oxide has been investigated in this context. This review will concentrate on the role of superoxide in human and experimental hypertension, paying particular attention to the potential sources of superoxide within the vasculature and discussing some of the molecular mechanisms surrounding its production and dismutation. We discuss what is known about the human superoxide dismutase enzymes. We conclude that the balance between nitric oxide and superoxide is more important than the absolute levels of either alone.

                Author and article information

                Clin Exp Pharmacol Physiol
                Clin. Exp. Pharmacol. Physiol
                Clinical and Experimental Pharmacology & Physiology
                John Wiley and Sons Inc. (Hoboken )
                24 January 2017
                February 2017
                : 44
                : 2 ( doiID: 10.1111/cep.2017.44.issue-2 )
                : 305-312
                [ 1 ] Laboratory of Veterinary PharmacologyAzabu University Sagamihara KanagawaJapan
                [ 2 ] Clinical NutritionChiba University Hospital ChibaJapan
                Author notes
                [* ] Correspondence

                Fumitoshi Asai, DVM, PhD, Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.

                Email: asai@

                © 2016 The Authors. Clinical and Experimental Pharmacology and Physiology Published by John Wiley & Sons Australia, Ltd.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                Page count
                Figures: 3, Tables: 2, Pages: 8, Words: 5252
                Funded by: Azabu University
                Original Article
                Original Articles
                Custom metadata
                February 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.5 mode:remove_FC converted:09.02.2017


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