Objective: The 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.
Methods: Adenosine in the dialysate collected during perfusion with Tyrode's solution containing 100μM 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.
Results: Fluvastatin (100μM), an inhibitor of low-density lipoprotein (LDL) oxidation, significantly increased the concentration of adenosine measured in the presence of 100μM 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, 50μM) or of protein kinase C (PKC; chelerythrine, 10μM). Fluvastatin (10-500μM) increased the level of AMP-primed dialysate adenosine in a concentration-dependent manner.
Conclusion: These 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.
Keywords: 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA); Adenosine; Ecto-5′-nucleotidase; Fluvastatin; Low-density lipoprotein (LDL); Protein kinase C (PKC).
Copyright © 2016. Published by Elsevier Inc.