Interference with Mitochondrial Activity Drives the On-Set of Cardiovascular Disease Following Long-Term Treatment with SGAs

The present study investigates the effects of neonatal serotonin modulation in female rats on cardiac parameters related to hemodynamics and oxidative metabolism in the mature animal.Female Wistar rat pups were administered daily subcutaneous injections of fluoxetine (Fx-treated group) or vehicle solution (Ct-group) from the 1st to 21st day of life. At 60 days of age, animals from both groups were either used for cardiovascular evaluation or sacrificed for tissue collection for biochemical assays.We found that body weight in the Fx-treated group was less than that in the control. When analyzing hemodynamic parameters (i.e., arterial blood pressure, heart rate—HR, sympathetic and vagal tonus, or intrinsic HR), we did not observe significant difference in the Fx-treated group. Evaluating oxidative stress in brainstem and heart by measuring carbonyl content and malondialdehyde—MDA formation, we observe a decrease in carbonyl content only in the Fx-treated group (60.3%, in brainstem; 58.2%, in heart), without difference in the MDA levels. This observation is consonant with an increase in superoxide dismutase—SOD and catalase—CAT activity in brainstem and heart in the Fx-treated group (SOD: 82.7% and CAT: 23.7 in brainstem; SOD: 60.6%, and CAT: 40.7 in heart), with no changes in glutathione S-transferase activity and reduced glutathione levels. With regard to oxidative metabolism markers, citrate synthase activity was higher in brainstem in the Fx-treated group (20%).Our data suggest that serotonin modulation by Fx-treatment at an early age does not induce hemodynamic alteration, although it modulates oxidative metabolism in cardiac-related tissues.