High Fructose-Induced Hypertension and Renal Damage Are Exaggerated in Dahl Salt-Sensitive Rats via Renal Renin-Angiotensin System Activation.

Abstract

BackgroundHigh‐fructose diet (HFr) induces hypertension and renal damage. However, it has been unknown whether the HFr‐induced hypertension and renal damage are exaggerated in subjects with salt sensitivity. We tested impacts of HFr in Dahl salt‐sensitive (DS) and salt‐resistant (DR) rats.Methods and ResultsMale DS and DR rats were fed control diet or HFr (60% fructose) with normal‐salt content. After 12 weeks, plasma and urinary parameters, renal histological characteristics, and renal expression of renin‐angiotensin system components were examined. Furthermore, effects of renin‐angiotensin system inhibitors were also examined in DS rats fed the HFr. HFr elevated blood pressure in DS rats but not in DR rats. HFr increased urinary albumin and liver type fatty acid binding protein excretions in both rats, but the excretions were exaggerated in DS rats. HFr increased plasma lipids and uric acid in both rats, whereas HFr increased creatinine clearance in DS rats but not DR rats. Although HFr decreased plasma renin activity in DS rats, HFr‐induced glomerular injury, afferent arteriolar thickening, and renal interstitial fibrosis were exaggerated in DS rats. HFr increased renal expression of angiotensinogen, renin, (pro)renin receptor, angiotensin‐converting enzyme, and angiotensin II type 1 receptor in DS rat, whereas HFr increased only angiotensin‐converting enzyme expression and decreased renin and angiotensin II type 1 receptor expressions in DR rats. Enalapril and candesartan attenuated the HFr‐induced hypertension, albuminuria, glomerular hyperfiltration, and renal damage in DS rats.ConclusionHFr‐induced hypertension and renal damage are exaggerated in DS rats via renal renin‐angiotensin system activation, which can be controlled by renin‐angiotensin system inhibitors.