Role of nitric oxide during early phase myocardial ischemic preconditioning in rats.
BACKGROUND
To date, there have been no reports on altered nitric oxide (NO) content in ischemia/reperfusion with regard to in vivo preconditioning procedures. These studies are important for understanding the mechanisms of NO during early myocardial ischemic preconditioning. The aim of the present study was to investigate the mechanisms of NO during early myocardial ischemic preconditioning by measuring levels of NO and cyclic guanosine monophosphate (cGMP), as well as activity of nitric oxide synthase (NOS) in ischemia/reperfusion with respect to preconditioning in rats.


METHODS
Sixty-six female Sprague-Dawley rats were randomly divided into four groups: ischemic preconditioning group (IP), ischemia/reperfusion group (I/R), control group (CON), and preconditioning procedure group (PC). In the PC group, rats were further divided into PC1-, PC1 +, PC2-, PC2 +, PC3-, and PC3 + subgroups. Rats underwent left coronary artery occlusion and reperfusion, and subsequently, NOS activity and levels were assessed with spectrophotometric analysis. cGMP contents were measured with radioimmunoassay.


RESULTS
The level of NO and cGMP, as well as the activity of NOS, were significantly higher in the IP group compared to the I/R and CON groups (P < 0.05). During preconditioning prior to prolonged ischemia, NO and cGMP levels varied markedly with ischemia and reperfusion. The levels of NO repeatedly increased when the heart was exposed to three episodes of 5-minute ischemia, and were almost completely reversed during each reperfusion period. NO and cGMP levels were significantly different between the 5-minute period of ischemia and the same period of reperfusion during preconditioning.


CONCLUSIONS
NO plays an important role during early phase myocardial ischemic preconditioning in rats. NO and cGMP could be triggers and mediators of early phase myocardial ischemic preconditioning. Altered NOS activity following ischemic stress could be the primary inducer of higher NO levels detected. NO and cGMP fluctuations might be the trigger for protection during early phase myocardial ischemic preconditioning.
Han
Hong-guang
HG
Department of Cardiovascular Surgery, Xijing Hospital of Fourth Military Medical University, Xi'an, Shaanxi, China. Hanxiyao@163.com
Wang
Zeng-wei
ZW
Zhang
Nan-bin
NB
Zhu
Hong-yu
HY
D000818:Animals; D006152:Cyclic GMP / Q000032:analysis; D005260:Female; D019157:Ischemic Preconditioning, Myocardial; D009569:Nitric Oxide / Q000032:analysis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP