Ischaemia or reperfusion: which is a main trigger for changes in nitric oxide mRNA synthases expression?
OBJECTIVE
To investigate alterations in endothelial nitric oxide synthase and inducible nitric oxide synthase mRNA expressions and nitric oxide release in the myocardium during ischaemia/reperfusion and determine whether these changes are ischaemic and/or reperfusion dependent.


METHODS
Isolated rat hearts were perfused by a modified Langendorff system. Following 1 h of global cardioplegic ischaemia, left ventricle haemodynamic parameters were recorded at baseline and during 30 min of reperfusion. Levels of endothelial, inducible nitric oxide synthases mRNA expression and nitric oxide release were measured at baseline, after ischaemia and at 30 min of reperfusion.


RESULTS
Global cardioplegic ischaemia caused a significant depression of left ventricular function and a decrease of coronary flow. Postischaemic intensities of the endothelial nitric oxide synthase mRNA bands were significantly lower than at baseline (P < 0.01). There were no significant differences in endothelial nitric oxide synthase mRNA band intensities immediately after ischaemia compared to the end of reperfusion, nor between the intensities of inducible nitric oxide synthase mRNA bands at baseline, at end of ischaemia and at end of reperfusion. Nitric oxide in the myocardial effluent was below detectable levels at all measured points.


CONCLUSIONS
Ischaemic injury causes down-regulation of endothelial nitric oxide synthase mRNA expression, which is then associated with reduction of coronary flow during reperfusion, representing one possible mechanism of ischaemia/reperfusion injury. We did not find expected elevations of inducible nitric oxide synthase mRNA expression during ischaemia or reperfusion and we suggest that ischaemia/reperfusion injury is not associated with nitric oxide overproduction.
Pevni
D
D
Department of Cardiothoracic Surgery, Tel Aviv University, Tel Aviv, Israel.
Frolkis
I
I
Shapira
I
I
Schwartz
D
D
Schwartz
I F
IF
Chernichovski
T
T
Lev-Ran
O
O
Sharony
R
R
Uretzky
G
G
D000818:Animals; D004730:Endothelium, Vascular / Q000201:enzymology; D006324:Heart Arrest, Induced / Q000379:methods; D008297:Male; D017202:Myocardial Ischemia / Q000201:enzymology; D015425:Myocardial Reperfusion / Q000379:methods; D009206:Myocardium / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000032:analysis*; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018487:Ventricular Dysfunction, Left / Q000201:enzymology / Q000503:physiopathology
D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II