Abstract
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. 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. 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 1α (69.5±1.5 pg/mg) and PGE 2 (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 A 2 (cPLA 2) (174.8±0.5%), COX2 (446.2±0.9%), PGI 2 synthase (201.8±1.1%) and PGE 2 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). 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.
Original language | English (US) |
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Pages (from-to) | 345-355 |
Number of pages | 11 |
Journal | Cardiovascular research |
Volume | 65 |
Issue number | 2 |
DOIs | |
State | Published - Feb 1 2005 |
Externally published | Yes |
Keywords
- Cyclooxygenase
- Infarction
- Phospholipases
- Prostaglandins
- Statins
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)