Insulin resistance and impaired endothelium-dependent renal vasodilatationin fructose-fed hypertensive rats

We investigated the contribution made by hyperinsulinemia and endothelial d ysfunction to the hypertension of rats that had received 10% fructose in th eir drinking water for 12 weeks. As control animals with endothelial dysfun ction, we used streptozotocin-induced diabetic rats. Measurements were made at 12 weeks after the start of fructose feeding or a single streptozotocin injection. Systolic blood pressure was greater in fructose-fed rats than i n either streptozotocin-diabetic rats or age-matched controls. By compariso n with the age-matched controls, the plasma levels of glucose, triglyceride , high density lipoprotein cholesterol, low density lipoprotein cholesterol and free fatty acids were all significantly raised in both fructose-fed ra ts and streptozotocin-diabetic rats, The plasma insulin was significantly r aised in fructose-fed rats, whereas it was significantly lowered in strepto zotocin-diabetic rats. The vasodilatation induced in the perfused kidney by acetylcholine was weaker in both fructose-fed rats and streptozotocin-diab etic rats than in the age-matched controls and these weakened responses wer e further attenuated by indomethacin. Acetylcholine increased the nitrite a nd nitrate (NO2- and NO3-) levels in the renal perfusate in age-matched con trols. This effect was much weaker in the two experimental groups. These re sults suggest that endothelial dysfunction in fructose-fed rats and strepto zotocin-diabetic rats may be due to a decreased synthesis of nitric oxide a t least in the perfused kidney. It is further suggested that hyperinsulinem ia is more important than endothelial dysfunction as a cause of hypertensio n in fructose-fed rats.