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

The 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 F_2α 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.