Development and characteristics of a new strain of obese hyperinsulinemic and hyperlipidemic dam salt-sensitive rat: The Dahl salt-sensitive/NIH-corpulent rat

A new congenic rat strain, the Dahl salt-sensitive/ NIH-corpulent (DSS/N-cp) rat, has been developed to study the role of obesity and type of dietary carbohydrate in the development of hypertension and its complications. Three groups (n = 6) of young male obese and lean DSS/N-cp rats were fed diets containing either 54% sucrose, 18% sucrose plus 36% starch, or 54% starch, with 0.1% dietary sodium for 12 weeks. Regardless of the diet, obese and lean rats showed mildly elevated systolic blood pressure (SBP), being significantly higher in obese than in lean rats (SBP 156 ± 5 mm Hg υ 141 ± 3 mm Hg, P< .05). However, SBP was not different between the three diet groups. Levels of serum insulin, triglyceride, and cholesterol as well as urinary protein excretion were significantly higher in obese than in lean rats. Obese rats fed the sucrose diets as compared to the starch diet, had higher serum insulin and lipid levels, but had lower body weights and higher serum creatinine levels. Histopathologic examination of tissues from different organs revealed a vasculopathy seen almost exclusively in obese rats fed the sucrose diets. Vascular lesions were characterized by subintimal fibrin deposition, fibrinoid necrosis, and cell proliferation with “onion skinning” in small arteries and arterioles of kidneys, intestine, pancreas, and testes. Vascular changes were similar to those previously reported in Dahl salt-sensitive rats fed a high salt diet. These data demonstrate the presence of mild hypertension with hyperinsulinemia and hyperlipidemia, which are expressed to a greater degree in the obese than in the lean phenotype. The results suggest that genetic factors associated with obesity, hypertension, and dietary sucrose interact in obese DSS/N-cp rats to produce renal and vascular damage, even with low dietary sodium intake.