Heme oxygenase and cardiac function in ischemic/reperfused rat hearts.
We investigated whether the expression of heme oxygenase (HO) isozymes was related to the occurrence of ventricular fibrillation (VF) induced by ischemia/reperfusion in nondiabetic and diabetic myocardium. To study the role of HO-1 and HO-2 mRNA expression in VF, isolated hearts obtained from nondiabetic and 8-week diabetic rats were subjected to 30 min of ischemia followed by 2 h of reperfusion. Expression of HO-1 and HO-2 mRNA was studied in fibrillated and nonfibrillated myocardium using Northern blotting and reverse transcription polymerase chain reaction (RT-PCR). The effect of zinc protoporphyrin IX (Zn-PPIX), a potent inhibitor of HO activity, on HO activity was also studied in ischemic/reperfused hearts. Upon reperfusion, an expression of HO-1 was observed in nonfibrillated myocardium. HO-1 mRNA expression was significantly reduced in hearts showed VF. Zn-PPIX (5 microM) treatment reduced HO activity from its control values of 398+/-27 (in nondiabetics) and 370+/-20 pmol bilirubin/h (in diabetics) to 69+/-14 (in nondiabetics, p<.05) and 60+/-11 pmol bilirubin/h (in diabetics, p<.05), respectively, and all hearts, upon reperfusion, showed VF in both nondiabetic and diabetic subjects. HO-2 expression was unchanged in nonfibrillated and fibrillated myocardium. Postischemic function showed no correlation with the expression of these genes. Our data show that the mechanism(s) of ischemia/reperfusion-induced VF involves the downregulation of HO-1 mRNA and a reduction in HO activity. Furthermore, the mechanism(s) of VF at molecular level involving HO isozymes does not show a significant difference between nondiabetics and diabetics.
Csonka
C
C
Department of Pharmacology, School of Medicine, Debrecen, Hungary.
Varga
E
E
Kovacs
P
P
Ferdinandy
P
P
Blasig
I E
IE
Szilvassy
Z
Z
Tosaki
A
A
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics; D008297:Male; D017202:Myocardial Ischemia / Q000201:enzymology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000201:enzymology*; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2