Chronic Intermittent Hypoxia Protects the Rat Heart Against Ischemic/Reperfusion Injury by Modulating Apoptosis: A Possible Role for Endogenous Nitric Oxide

Background: Intermittent hypoxia has been shown to provide myocardial protection
against ischemia/reperfusion injury. Cardiac myocyte loss through apoptosis has
been reported in ischemia/reperfusion injury. The role of nitric oxide (NO) in
modulating apoptosis in rats exposed to chronic intermittent hypoxia is controversial.
The aim of the present work is to investigate the possible role of nitric oxide synthase
inhibition on modulation of apoptosis in ischemic- reperfused isolated hearts of rats
exposed to chronic intermittent hypoxia. Methods: Adult male albino rats were used
and exposed to normaxic or hypoxic conditions as follows: Group I: Normoxic
conditions (normoxia group), Group II : Chronic intermittent hypoxia (CIH group)
(10% O2 and 90% N2) for 8 hours daily, then to normal environmental air for the
rest of the day, 5 days/ week for 4 weeks, Group III: Normoxic conditions and treated
with L-NAME (10 mg/kg B.W.via intra-gastric route) (L-NAME group), Group IV:
Chronic intermittent hypoxia and treated with L-NAME (CIH + L-NAME group) They
had daily L-NAME(10 mg/kg B.W.via intra-gastric route) and exposed to the chronic
intermittent hypoxia in the same way and duration as rats of group II. Isolated
perfused hearts were subjected to 30 minutes of global ischemia followed by 30
minutes reperfusion. Left ventricular developed pressure (LVDP), contractility
(dp/dt), and heart rate(HR) were recorded continuously. Expression of Bcl-2 in the
myocardium was detected. Results: The parameters of functional recovery were
improved in CIH group with significant increase in Bcl-2 expression as compared to
normoxia group. Treatment with L-NAME led to attenuation of improved post–
ischemic recovery of the ventricular function provided by chronic intermittent
hypoxia with significant reduction in Bcl-2 expression compared with CIH group.
Conclusion: adaptation to chronic intermittent hypoxia increases cardiac tolerance to
ischemia/reperfusion. This protective effect was associated with increased expression
of the antiapoptotic protein Bcl-2, that limits the apoptotic cell death in the
myocardium following the ischemic/reperfusion insult. L-NAME attenuated both the
improved recovery of cardiac function and the expression of antiapoptotic protein
Bcl-2 induced by CIH.