Troglitazone corrects metabolic changes but not vascular dysfunction in dietary-obese rats.
Insulin resistance has been attributed to the defect in vascular function associated with obesity, type 2 diabetes and dyslipidaemia. We have investigated vascular effects of chronic (3-week) administration of troglitazone on female Wistar rats with moderate dietary obesity. Compared with lean controls, untreated obese rats had significantly higher body weights, fat pad masses, plasma triglycerides, free fatty acids and leptin levels (for all P < 0.01). These metabolic changes were corrected by troglitazone treatment. In mesenteric arteries, responses to noradrenaline or KCl were similar in all groups. However, in noradrenaline-preconstricted arteries, vasorelaxations to acetylcholine and insulin were significantly (50-60% less than in lean, P < 0.001) attenuated in both untreated and troglitazone-treated obese rats. Relaxations to sodium nitroprusside showed similar but lesser impairment in both untreated and troglitazone-treated obese animals. Our data show that although troglitazone markedly improved obesity-induced metabolic changes, it failed to correct vascular dysfunction associated with obesity in female Wistar rats.
Diabetes and Endocrinology Research Unit, Department of Medicine, University of Liverpool, UCD, Daulby Street, L69 3GA, Liverpool, UK. naderali@liverpool.ac.uk
E K
EK
Naderali
L C
LC
Pickavance
J P
JP
Wilding
P J
PJ
Doyle
G
G
Williams
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D004032:Diet / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D020738:Leptin / Q000097:blood; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014280:Triglycerides / Q000097:blood; D000077288:Troglitazone; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D001786:Blood Glucose; D002839:Chromans; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D013844:Thiazoles; D045162:Thiazolidinediones; D014280:Triglycerides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D011189:Potassium Chloride; D000077288:Troglitazone; D000109:Acetylcholine; D009638:Norepinephrine