Fluvastatin, an HMG-CoA reductase inhibitor, facilitate adenosine production in the rat hearts via activation of ecto-5′-nucleotidase

• Fluvastatin, an inhibitor of LDL oxidation, can increased adenosine production.
• Adenosine increased via activation of ecto-5′-nucleotidase in the ventricular myocardium.
• Fluvastatin increases in adenosine production mediated by stimulation of α1-adrenoceptors.

ObjectiveThe present study was examined whether fluvastatin, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, can increase the production of interstitial adenosine via activation of ecto-5′-nucleotidase in the ventricular myocardium, with use of microdialysis techniques in in situ rat hearts.MethodsAdenosine in the dialysate collected during perfusion with Tyrode's solution containing 100 μM AMP (through the probe) originated from the hydrolysis of AMP catalyzed by endogenous ecto-5′-nucleotidase, so that the level of adenosine reflected the activity of ecto-5′-nucleotidase in this tissue.ResultsFluvastatin (100 μM), an inhibitor of low-density lipoprotein (LDL) oxidation, significantly increased the concentration of adenosine measured in the presence of 100 μM AMP (i.e., the activity of ecto-5′-nucleotidase) by 154.7 ± 16.0% (n = 6, P < 0.05), an increase which inhibited an antagonist of the α1-adrenoceptor (prazosin, 50 μM) or of protein kinase C (PKC; chelerythrine, 10 μM). Fluvastatin (10–500 μM) increased the level of AMP-primed dialysate adenosine in a concentration-dependent manner.ConclusionThese results indicate that fluvastatin increases in adenosine concentrations in the dialysate which resulted from activation of PKC, mediated by stimulation of α1-adrenoceptors, through activation of ecto-5′-nucleotidase.