Early atorvastatin administration suppresses the oxygen-activating ability of rat neutrophils during monocrotalinin-induced pulmonary arterial hypertension (PAH)

Abstract

Methods: Eighty male rats (200-250 g) were subjected to subcutaneous injection MCT 60 mg\kg and monitored for up to 8 weeks. Animals received atorvastatin (40 mg\kg) daily for the throughout the experiment. All animals with PAH were divided into groups: preventive and late administration of the drug (A0 and A14, respectively) depending on the initiation of therapy in relation to the development of PAH. Rats A0 received atorvastatin immediately after administration of monocrotaline. Rats A14 received atorvastatin 14 days after injection MCT. The control group were administered only MCT without atorvastatin. The oxygen-activating ability of rat neutrophils (ROS) was determined by the method of luminol-dependent chemiluminescence in peripheral blood. The ability of cells to generate myeloperoxidase and lysozyme was studied under conditions of phagocytosis stimulation with the chemotactic fMLP peptide.

Results: The formation of superoxide anion radicals decreased in the A0 group compared to A14 and the control was 2.1 times (p <0.05) after 8 weeks. At the same time, there were not statistically differ in the number of leukocytes and neutrophils in the studied groups respectively. A significant decrease in the production of myeloperoxidase and lysozyme from neutrophils into the extracellular medium was found. In group A0, the total generation of these enzymes decreased by 82 ± 12% (p <0.05), and in group A14 by 48 ± 7% compared with the control group.

Conclusions: Preventive administration atorvastatin (40 mg / kg) reduces the oxygen-activating enzymatic activity of rat neutrophils.