Lawrence W Dobrucki, Leszek Kalinowski, Iwona T Dobrucki, Tadeusz Malinski
Med Sci Monit 2001; 7(4): BR622-627
BACKGROUND: There is increasing evidence that loss of endothelium-derivedNO is a major factor in cardiovascular complication events, and that NO might exert antiatheroscleroticactions. The beneficial effects of HMG CoA reductase inhibitors (statins) therapy in atherosclerosisoutweigh those expected from simply lowering low-density lipoprotein (LDL) cholesterol, and may be relatedto the direct action in the endothelium. Based on these concepts, in the studies described here, theeffect of new statin derivatives on nitric oxide (NO) and superoxide (O2-) release in bovine endothelialcells was tested.MATERIAL AND METHODS: Highly sensitive electrochemical NO and O2--microsensors wereplaced near the surface of endothelial cells, and the concurrent kinetics of NO and O2-- release weremeasured in situ.RESULTS: All tested statins stimulated NO release. The peak concentration of NO afterstimulation with 1 Kmol/l Lovastatin, 1 Kmol/l Atorvastatin, 1 Kmol/l Pravastatin, or 1 Kmol/l Simvastatinwas about 77%, 73%, 72%, and 44% lower, respectively, as compared with the NO peak concentration afterstimulation with 1 Kmol/l calcium ionophore A23187 (receptor-independent agonist). The tested statinsstimulated NO release in a modest way, which resulted in diminishing O2- generation during activationof nitric oxide synthase. Moreover, the kinetics of O2- release after administration of the statins suggestedthat these compounds may also scavenge O2-. The NO/O2- peak concentration ratio after the NOS agonistsadministration was as follows: 7.51 for CaI, 6.56 for Lovastatin, 6.00 for Atorvastatin, 4.17 for Pravastatinand 6.25 for Simvastatin.CONCLUSIONS: The tested statins, i.e. Lovastatin, Atorvastatin, Pravastatinand Simvastatin demonstrate variable potency to enhance the NO/O2- concentration ratio after stimulationof NOS, resulting in an increase of NO bioavailability in endothelial cells.
Keywords: statins, Endothelium, Nitric Oxide, superoxide