Rosuvastatin treatment reverses impaired coronary artery vasodilation in fructose-fed, insulin-resistant rats.
Insulin resistance (IR) impairs vascular responses in coronary arteries, but mechanisms of dysfunction and approaches to treatment remain unclear. We examined the ability of a new 3-hydroxy-methylglutaryl coenzyme A reductase inhibitor, rosuvastatin, to reverse reduced dilator responses in rats made IR by feeding a fructose-rich diet (FF). Sprague-Dawley rats were randomized to control (normal rat diet) or FF. After 1 wk, rats received rosuvastatin (2 mg/kg) or placebo (saline) subcutaneously for 5 wk. Biochemical measurements and in vitro functional studies of small coronary arteries were performed. Fasting insulin and triglyceride (TG) levels were markedly increased in FF-placebo rats compared with other groups. Rosuvastatin treatment of FF rats normalized TG and modestly decreased insulin levels. ACh-induced dilator responses were depressed in arteries from FF-placebo rats. This impairment was due to decreased responses via calcium-dependent K channels (K(Ca)). Rosuvastatin treatment of FF rats completely reversed the response to ACh to normal levels. Moreover, this recovery in function was due to an improvement in vasodilation via K(Ca). Thus rosuvastatin treatment of IR rats normalizes coronary vascular dilator responses by improving the K(Ca) function.
Miller
Allison W
AW
Dept. of Physiology and Pharmacology, Wake Forest Univ. School of Medicine, Hanes 1050, Medical Center Blvd., Winston-Salem, NC 27157, USA.
Tulbert
Christina D
CD
Busija
David W
DW
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002784:Cholesterol / Q000097:blood; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000503:physiopathology*; D005464:Fluorobenzenes / Q000494:pharmacology*; D005632:Fructose / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D005464:Fluorobenzenes; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D011743:Pyrimidines; D013449:Sulfonamides; D014280:Triglycerides; D014665:Vasodilator Agents; D005632:Fructose; D000068718:Rosuvastatin Calcium; D002784:Cholesterol; D000109:Acetylcholine