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

Clin Exp Pharmacol Physiol. 2017 Feb;44(2):305-312. doi: 10.1111/1440-1681.12700.

Abstract

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-Leprfa/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 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.

Keywords: WBN/Kob-Leprfa/fa rat; high-sodium diet; salt-sensitive hypertension; type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Congenic
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiopathology
  • Blood Glucose / analysis
  • Blood Pressure / drug effects*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Hypertension / etiology
  • Insulin / blood
  • Kidney / pathology
  • Kidney / physiopathology
  • Male
  • Obesity / blood
  • Obesity / complications
  • Obesity / physiopathology*
  • Rats, Wistar
  • Sodium Chloride, Dietary / adverse effects*
  • Vasoconstriction / drug effects*

Substances

  • Blood Glucose
  • Insulin
  • Sodium Chloride, Dietary