Estradiol attenuates cardiac apoptosis and modulates cardiovascular remodeling in ovariectomized female rats with 6-hydroxydopamine-induced parkinsonism

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and reduced striatal dopamine concentrations. In addition to its characteristic motor manifestations, PD is associated with nonmotor complications, including cardiovascular autonomic dysfunction, orthostatic and postprandial hypotension, and blood pressure instability. The lower prevalence of PD in women has prompted investigation into the potential protective effects of female sex hormones. In this study, we evaluated cardiovascular function, autonomic modulation, cardiac and vascular morphology, and apoptosis in ovariectomized female rats with 6-OHDA-induced parkinsonism treated with estradiol. Wistar rats underwent bilateral ovariectomy and received estradiol (1 mg/kg) or almond oil as the vehicle for 13 consecutive days. Seven days after ovariectomy, 6-OHDA or SHAM vehicle was infused bilaterally into the SNpc. Six days later, the animals underwent femoral artery catheterization, and mean arterial pressure (MAP) and heart rate (HR) were recorded after 24 h. The 6-OHDA lesion reduced striatal dopamine concentrations by more than 50%, confirming the induction of parkinsonism. No significant group differences were detected in MAP, HR, autonomic variability, or baroreflex sensitivity. However, parkinsonism reduced left ventricular wall thickness, increased apoptosis in both ventricles, and decreased cardiac and aortic collagen content. Estradiol increased left ventricular wall thickness and partially attenuated ventricular apoptosis and the parkinsonism-associated alteration in aortic elastin. These findings indicate that 6-OHDA-induced parkinsonism produces cardiac and aortic structural alterations that are not reflected in basal cardiovascular or autonomic measurements and, estradiol may modulate selected cardiac alterations. Although the underlying mechanisms and translational relevance require further investigation, our findings suggest potential clinical relevance for postmenopausal women with Parkinson's disease.