Cardioprotection mediated by rosiglitazone, a peroxisome proliferator-activated receptor gamma ligand, in relation to nitric oxide.
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 of WT mice received the NOS inhibitor L-NNA (100 micromol/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).


CONCLUSIONS
These results suggest that the cardioprotective effect of the PPARgamma agonist rosiglitazone is mediated via NO by phosphorylation of eNOS.
Gonon
Adrian T
AT
Dept. of Cardiology, Karolinska University Hospital, Solna, 17176, Stockholm, Sweden. adrian.gonon@medks.ki.se
Bulhak
Aliaksandr
A
Labruto
Fausto
F
Sjöquist
Per-Ove
PO
Pernow
John
J
D000818:Animals; D015153:Blotting, Western; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000494:pharmacology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III