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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., (Copyright © 2016. Published by Elsevier Inc.)

Examined in the present study, allopurinol are xanthine oxidase inhibitors for use in rat hearts in vivo dialysis technology and ventricular myocardial intersitial adenosine production can increase. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rat hearts and the tissue in the vicinity of the dialysis was perfused with Tyrode's solution containing adenosine 5'-monophosphate (AMP) through the dialysis probe at a rate of 1.0 ml/min to assess the activity of ecto-5'-nucleotidase. Allopurinol (10 μM) significantly increased the level of adenosine in rat heart dialysate (n=6, p<0.05), which was inhibited by chelerythrine, 10 μM, an antagonist of protein kinase C (PKC). Another free radical scavenger, coenzyme Q10 (CoQ10, 100 μM) or ascorbic acid (Vitamin C; 100 μM) also increased adenosine production. In addition, allopurinol enhanced the diacylglycerol (DAG; 50 μM)-induced also increases in adenosine production by 71.5±12.0% (n=6, P<0.05), to a level significantly (P<0.05) greater than the increase caused by DAG alone (33.0±10.6%). In the presence of allopurinol (10 μM), a marked elevation of AMP-primed dialysate adenosine in ischemia/reperfused rat hearts was observed. Free radical generation may suppress adenosine production via activation of PKC. The results suggest that oxidative stress may cause inactivation of nucleotidase, adenosine production in rat heart. [ABSTRACT FROM AUTHOR]