Treatment of cardiovascular dysfunction associated with the metabolic syndrome and type 2 diabetes.
Our previous studies have shown vascular dysfunction in small coronary and mesenteric arteries in Zucker obese rats, a model of the metabolic syndrome, and Zucker Diabetic Fatty (ZDF) rats, a model of type 2 diabetes. Because of their lipid lowering action and antioxidant activity, we predicted that treatment with Rosuvastatin, an HMG-CoA reductase inhibitor (statin) or Enalapril, an angiotensin converting enzyme (ACE) inhibitor would improve vascular dysfunction associated with the metabolic syndrome and type 2 diabetes.


METHODS
20-week-old Zucker obese and 16-week-old ZDF rats were treated with Rosuvastatin (25 mg/kg/day) or Enalapril (20 mg/kg/day) for 12 weeks. We examined metabolic parameters, indices of oxidative stress and vascular dysfunction in ventricular and mesenteric small arteries (75-175 microm intraluminal diameter) from lean, Zucker obese and ZDF rats (untreated and treated).


RESULTS
Endothelial dependent responses were attenuated in coronary vessels from Zucker obese and ZDF rats compared to responses from lean rats. Both drugs improved metabolic parameters, oxidative stress, and vascular dysfunction in Zucker obese rats, however, only partial improvement was observed in ZDF rats, suggesting more aggressive treatment is needed when hyperglycemia is involved.


CONCLUSIONS
Vascular dysfunction is improved when Zucker obese and, to a lesser degree, when ZDF rats were treated with Rosuvastatin or Enalapril.
Oltman
Christine L
CL
Department of Veterans Affairs, Iowa City, Iowa 52246, USA. christine-oltman@uiowa.edu
Kleinschmidt
Travis L
TL
Davidson
Eric P
EP
Coppey
Lawrence J
LJ
Lund
Donald D
DD
Yorek
Mark A
MA
D000367:Age Factors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004656:Enalapril / Q000494:pharmacology* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D005227:Fatty Acids / Q000097:blood; D005464:Fluorobenzenes / Q000494:pharmacology* / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011924:Rats, Zucker; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D005227:Fatty Acids; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D014280:Triglycerides; D004656:Enalapril; D000068718:Rosuvastatin Calcium; D002784:Cholesterol