title: Increasing insulin sensitivity lowers blood pressure in the fructose-fed rat.
abstract: In the rat, simple carbohydrate feeding induces insulin resistance, and insulin resistance is associated with impaired endothelium dependent vasodilation. To determine if increasing insulin sensitivity corrects this defect of endothelial function, we evaluated the effects of an insulin-sensitizing agent, pioglitazone, on arterial pressure and in vitro vascular reactivity in three groups of Sprague Dawley rats: 1) control; 2) 60% fructose diet for 4 weeks; 3) 60% fructose diet plus pioglitazone (20 mg/kg daily, by oral gavage). Direct mean arterial pressure did not differ in Groups 1 (120 mm Hg +/- 2) and 2 (121 +/- 2) and was lower (P < .05) in Group 3 (112 +/- 2). In vitro uptake of tritiated glucose by adipocytes in response to insulin was reduced (P < .05) by fructose and increased (P < .01) by pioglitazone. In strips of thoracic aorta, norepinephrine-induced vasoconstriction and nitroprusside induced vasodilation did not differ among groups. However, in response to graded dose of acetylcholine, vasodilation was reduced (P < .05) by fructose; this was normalized by pioglitazone. In all groups, N(G)-nitro-L-arginine methyl ester (L-NAME) completely blocked acetylcholine-induced vasodilation. Thus, pioglitazone increased insulin sensitivity, lowered blood pressure, and normalized acetylcholine-induced vasodilation in insulin resistant, fructose-fed rats. Increasing insulin sensitivity may lower arterial pressure by augmenting endothelium dependent vasodilation.
authors.affiliation: Department of Medicine, Medical College of Wisconsin, Milwaukee, 53226, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Kotchen
authors.forename: S
authors.initials: S
authors.lastname: Reddy
authors.forename: H Y
authors.initials: HY
authors.lastname: Zhang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology*; D005632:Fructose / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D014662:Vasoconstrictor Agents; D005632:Fructose; D005947:Glucose; D000109:Acetylcholine; D000077205:Pioglitazone; D009638:Norepinephrine