Chronic corticosterone treatment increases myocardial infarct size in rats with ischemia-reperfusion injury.
Experiments were conducted to determine the effect of chronic elevations in corticosterone on myocardial infarct size. Male Sprague-Dawley rats were treated for 7-22 days with corticosterone. Plasma corticosterone concentrations averaged 0.8 +/- 0.3 in control and 14.9 +/- 1.2 micrograms/dl in corticosterone-treated conscious rats. Experiments were performed in anesthetized rats. After a 30-min control period, myocardial ischemia (30 min)-reperfusion (3 h) was performed in control and corticosterone-treated rats. Mean arterial pressure (+/-SE) in control rats during control, ischemia, and reperfusion periods averaged 111 +/- 4, 100 +/- 5, and 94 +/- 4 mmHg (n = 6), respectively. Chronic treatment with corticosterone increased mean arterial pressure in all three periods 128 +/- 6, 117 +/- 7, and 109 +/- 7 mmHg; n = 8; P < 0.05). Infarct size (as % area at risk) was significantly larger in rats with chronic elevations in corticosterone compared with control rats (77 +/- 2 vs. 51 +/- 5%, P < 0.05). Acute (2 h) blockade of the glucocorticoid type II receptors with mifepristone antagonized the increases in arterial pressure and infarct size produced by chronic administration of corticosterone. Neither mifepristone nor acutely administered corticosterone affected arterial pressure or infarct size in rats without chronic corticosterone treatment. The effect of chronic elevations in plasma corticosterone concentration to increase infarct size could contribute to the increased risk of cardiovascular disease in clinical conditions associated with elevated glucocorticoid levels.
Scheuer
D A
DA
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764, USA.
Mifflin
S W
SW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003345:Corticosterone / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000473:pathology*; D017202:Myocardial Ischemia / Q000139:chemically induced* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D013997:Time Factors
D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003345:Corticosterone