Insulin resistance and impaired endothelium-dependent renal vasodilatation in fructose-fed hypertensive rats.
We investigated the contribution made by hyperinsulinemia and endothelial dysfunction to the hypertension of rats that had received 10% fructose in their drinking water for 12 weeks. As control animals with endothelial dysfunction, 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 in either streptozotocin-diabetic rats or age-matched controls. By comparison 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 rats and streptozotocin-diabetic rats. The plasma insulin was significantly raised in fructose-fed rats, whereas it was significantly lowered in streptozotocin-diabetic rats. The vasodilatation induced in the perfused kidney by acetylcholine was weaker in both fructose-fed rats and streptozotocin-diabetic rats than in the age-matched controls and these weakened responses were further attenuated by indomethacin. Acetylcholine increased the nitrite and nitrate (NO2- and NO3-) levels in the renal perfusate in age-matched controls. This effect was much weaker in the two experimental groups. These results suggest that endothelial dysfunction in fructose-fed rats and streptozotocin-diabetic rats may be due to a decreased synthesis of nitric oxide at least in the perfused kidney. It is further suggested that hyperinsulinemia is more important than endothelial dysfunction as a cause of hypertension in fructose-fed rats.
Kamata
K
K
Department of Physiology and Morphology, Hoshi University, Tokyo, Japan. kamata@hoshi.ac.jp
Yamashita
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005632:Fructose / Q000008:administration & dosage*; D006439:Hemodynamics; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D007333:Insulin Resistance; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014664:Vasodilation / Q000187:drug effects
D009599:Nitroprusside; D005632:Fructose; D009569:Nitric Oxide; D013311:Streptozocin; D000109:Acetylcholine