Enhancement of post-ischemic myocardial function by chronic 17 beta -estradiol treatment: role of alterations in glucose metabolism.
This study was designed to assess the effects of chronic estrogen replacement therapy on mechanical function and glucose utilization in aerobic and post-ischemic hearts. Ovariectomized female rats were either untreated or were treated subcutaneously with 17 beta -estradiol (0.25 mg 21-day slow release pellets). After 14 days, when serum concentrations of 17 beta -estradiol were 3.8+/-0.8 and 148+/-15 pg/ml, respectively, hearts were isolated and perfused in working mode with Krebs-Henseleit solution containing 1.2 m m palmitate and 11 m m[5-(3)H/U-(14)C]glucose. Hearts were perfused aerobically (60 min) and then subjected to low-flow ischemia (0.5 ml/min, 60 min) followed by reperfusion (30 min). During reperfusion, hearts from rats treated chronically with 17 beta -estradiol had an improved (two-fold) recovery of mechanical function. 17 beta -estradiol (400 p m, 109 pg/ml), when present acutely in heart perfusate during ischemia and reperfusion, did not improve recovery. Chronic 17 beta -estradiol increased glucose oxidation during reperfusion as well as during aerobic perfusion but had no effect on glycolysis. Chronic 17 beta -estradiol also altered post-ischemic glycogen metabolism and increased glycogen content and glycogen synthase activity at the end of reperfusion. As stimulation of glucose oxidation has been shown previously to be cardioprotective, and as the enhanced rate of glucose oxidation was not simply a consequence of enhanced recovery of mechanical function, alterations in glycogen and glucose utilization may contribute to the direct cardioprotective effects of chronic estrogen treatment.
Fraser
H
H
Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada.
Davidge
S T
ST
Clanachan
A S
AS
D000818:Animals; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D020249:Hormone Replacement Therapy; D007279:Injections, Subcutaneous; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
D004958:Estradiol; D005947:Glucose