Chronic atorvastatin treatment weakens procontractile influence of NADPH oxidase derived ROS in systemic murine...

The beneficial effects of statins for cardiovascular system were widely described in various pathologies. However, much less is known about the effects of statins in healthy organism, especially in systemic resistance arteries. We aimed to evaluate the effect of chronic administration of atorvastatin, one of the most prescribed drugs, on the arterial functioning in various organs (brain, small intestine, skeletal muscle) of mice, including the procontractile influence of NADPH oxidase derived reactive oxygen species (ROS) as well as Rho-kinase. Mature male outbred ICR(CD-1) mice were administered with atorvastatin during 4 weeks (daily dose ⁓ 7 mg/kg), control animals drank water with its solvent DMSO (0.3% v/v). Basilar, sural and mesenteric arteries were studied by wire myography and/or qPCR. Atorvastatin treatment led to the reduction of contractile responses to thromboxane A2 receptor agonist U46619 in basilar arteries, but did not change responses of sural and mesenteric arteries to α1-adrenoceptor agonist methoxamine. Endothelium-dependent relaxation to acetylcholine was not altered in all studied arteries. Procontractile contribution of NADPH oxidase derived ROS was weakened in all arteries in atorvastatin group of animals, that was associated with the reduced procontractile influence of Rho-kinase in basilar arteries, but not sural and mesenteric. mRNA values of catalytic Nox2 and Nox4 subunits in mesenteric arteries were not changed due to atorvastatin treatment. Therefore, chronic atorvastatin treatment during one month affects the mechanisms regulating vascular tone in healthy mice, which must be taken into account when prescribing statin therapy to healthy people for preventive purposes.