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

Abstract

SummaryThe prevalence of type 2 diabetes mellitus (T2DM) 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 T2DM. 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 (WBKDF‐NS); (iv) WBKDF rats on HS diets (WBKDF‐HS). Neither WBKDF‐NS nor Wistar‐NS rats showed significant changes in SBP throughout the experiment, but both WBKDF‐HS and Wistar‐HS exhibited significant elevation of SBP, which was more prominent (P<.01) in WBKDF‐HS than in Wistar‐HS. Phenylephrine‐induced contractions of isolated thoracic aortic rings were significantly (P<.01) enhanced in WBKDF‐HS 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 WBKDF‐HS 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 F2α and sodium ions were observed in WBKDF‐HS than in Wistar‐HS. The current study demonstrated that WBKDF‐HS rats developed salt‐sensitive hypertension associated with vascular dysfunction. The WBKDF rat may be a useful model for investigating the etiology of hypertension with T2DM.

High-Salt Intake Ameliorates Hyperglycemia and Insulin Resistance in WBN/Kob-Leprfa/fa Rats: A New Model of Type 2 Diabetes Mellitus

“…These results suggest that hyperglycemia in the WBKDF rat is mainly due to hyperphagia [ 16 ]. However, our present and previous studies [ 9 ] found no significant differences in food consumption. Thus, inhibition of hyperglycemia by HS intake in WBKDF rats is unlikely due to reduced food and calorie intake.…”

“…The male WBKDF rat used in this study is a new metabolic syndrome model exhibiting obesity, dyslipidemia, and T2DM [ 4 – 6 , 8 ]. Recently, we found that HS intake produces salt-sensitive hypertension in WBKDF rats, suggesting this strain as a useful animal model of metabolic syndrome [ 9 ]. This encouraged us to examine the effects of HS intake on T2DM model rats with salt sensitivity.…”

“…According to our previous report [ 9 ], the HS diet containing 8% NaCl was demonstrated to be suitable for evaluating the long-term effects of HS in experimental animals [ 13 ]. As in the previous study [ 9 ], HS significantly increased SBP in WBKDF rats throughout the experiment. However, this salt-sensitive hypertension in WBKDF-HS was associated with the significant inhibition of hyperglycemia evident in WBKDF-NS rats.…”

“…Our previous study demonstrated that WBKDF-HS rats developed salt-sensitive hypertension associated with vascular dysfunction and increased oxidative stress [ 9 ]. To further validate WBKDF rats as a metabolic syndrome model, in the present study, we examined the effects of high-salt intake on glucose homeostasis in WBKDF rats in comparison with age-matched Wistar rats.…”

Characteristics of WBN/Kob diabetic fatty rats supplemented with a fructose-rich diet as a metabolic syndrome model: response to a GLP-1 receptor agonist

“…Systolic blood pressure (SBP) was monitored using a tail cuff blood pressure analyzer (BP98A-L, Softron, Tokyo, Japan) as described previously [ 36 ]. The rats were prewarmed for 15–20 min at 32°C to improve the detection of pulsation of the tail artery.…”