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Birnbaum, Y. et al.

Birnbaum, Ye, Rosanio, Tavackoli, Hu, Schwarz, Uretsky,

Prostaglandins mediate the cardioprotective effects of atorvastatin against ischemia-reperfusion injury.

OBJECTIVES: Statins attenuate myocardial ischemic injury by activating nitric oxide synthase (NOS). It is unknown whether cyclooxygenase-2 ( COX2), which mediates late ischemic preconditioning, also mediates statins-induced cardioprotection. We investigated the involvement of the prostaglandins and NOS in the cardioprotective effect of atorvastatin (ATV) in the rat. METHODS: Sprague-Dawley rats were randomized to a 3-day oral treatment with ATV 10 mg/kg, valdecoxib, a selective COX2 inhibitor (VAL) 3 mg/kg, ATV+VAL or water alone. Rats underwent 30-min myocardial ischemia followed by 4-h reperfusion. RESULTS: Infarct size was smaller in the ATV group (31.3+/-1.9%) than controls (44.5+/-3.1%; p=0.011) and VAL (44.5+/-3.1%; p=0.008). VAL attenuated the protective effect of ATV when administered together (40.2+/-2.5%). ATV pretreatment increased myocardial content of 6-keto-PGF(1alpha) (69.5+/-1.5 pg/mg) and PGE2 (57.9+/-0.6 pg/mg) compared with controls (16.2+/-0.2 and 42.1+/-2.0 pg/mg, respectively) and ATV+VAL (15.8+/-0.3 and 39.9+/-1.9 pg/mg, respectively). ATV increased myocardial content of cytosolic phospholipase A2 (cPLA2) (174.8+/-0.5%), COX2 (446.2+/-0.9%), PGI2 synthase (201.8+/-1.1%) and PGE2 synthase (122+/-0.7%), whereas ATV+VAL did not (123.0+/-7.9%, 93.8+/-8.5%, 103.0+/-1.6% and 99.0+/-0%, respectively). ATV did not change the myocardial content of eNOS and nNOS, but increased the concentration of phosphorylated eNOS (231.8+/-2.4%) and iNOS (154.5+/-1.2%). This effect was not blocked by coadministration of VAL (231.5+/-3.0% and 154.5+/-1.8%, respectively). CONCLUSIONS: Our results suggest that the prostaglandins are essential for mediating the myocardial protective effects of ATV and their production is downstream to eNOS phosphorylation and iNOS.[1]

References

Prostaglandins mediate the cardioprotective effects of atorvastatin against ischemia-reperfusion injury. Birnbaum, Y., Ye, Y., Rosanio, S., Tavackoli, S., Hu, Z.Y., Schwarz, E.R., Uretsky, B.F. Cardiovasc. Res. (2005) [Pubmed]

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