Activation of peroxisome proliferator-activated receptor
(PPAR) gamma protects from myocardial ischemia/reperfusion injury. The
aim of the study was to investigate whether the cardioprotective effect of
PPARgamma is related to nitric oxide (NO).
Methods
Wild type (WT) and endothelial
NO synthase (eNOS) knockout (KO) mice received 3 mg/kg of the
PPARgamma agonist rosiglitazone or vehicle (n = 6–9 in each group) i. p.
45 min before anesthesia. The hearts were isolated, perfused in a Langendorff
mode and subjected to global ischemia and 30 min reperfusion. The
hearts of another two groups ofWT mice received the NOS inhibitor L-NNA
(100 ìmol/l) or vehicle in addition to pre-treatment with vehicle or rosiglitazone.
Results
In the WT heart, rosiglitazone increased the recovery of left
ventricular function and coronary flow following ischemia in comparison
with the vehicle group.L-NNA did not affect recovery per se but significantly
blunted the improvement in the recovery of left ventricular function induced
by rosiglitazone. In the KO group rosiglitazone suppressed the recovery of
myocardial function following ischemia. Expression of eNOS was not affected,
but phosphorylated eNOS was significantly increased by rosiglitazone
in the WT hearts (P < 0.05).
Conclusion
These results suggest that the
cardioprotective effect of the PPARgamma agonist rosiglitazone is mediated
via NO by phosphorylation of eNOS.
Key words peroxisome proliferator-activated receptor gamma - nitric
oxide - ischemia - reperfusion - heart