RESUMO
Abstract Aims Although reduced life expectancy in Parkinson's Disease (PD) patients has been related to severe cardiac arrhythmias due to autonomic dysfunctions, its molecular mechanisms remain unclear. To investigate the role of cardiac β1-Adrenergic (β1AR) and A1-Adenosine (A1R) receptors in these dysfunctions, the pharmacological effects of stimulation of cardiac β1AR (isoproterenol, ISO), in the absence and presence of cardiac β1AR (atenolol, AT) or A1R (1,3-dipropyl-8-cyclopentyl xanthine, DPCPX) blockade, on the arrhythmias induced by Ischemia/Reperfusion (CIR) in an animal PD model were studied. Methods PD was produced by dopaminergic lesions (confirmed by immunohistochemistry analysis) caused by the injection of 6-hydroxydopamine (6-OHDA, 6 μg) in rat striatum. CIR was produced by a surgical interruption for 10 min followed by reestablishment of blood circulation in the descendent left coronary artery. On the incidence of CIR-Induced Ventricular Arrhythmias (VA), Atrioventricular Block (AVB), and Lethality (LET), evaluated by Electrocardiogram (ECG) analysis, the effects of intravenous treatment with ISO, AT and DPCPX (before CIR) were studied. Results VA, AVB and LET incidences were significantly higher in 6-OHDA (83%, 92%, 100%, respectively) than in control rats (58%, 67% and 67%, respectively). ISO treatment significantly reduced these incidences in 6-OHDA (33%, 33% and 42%, respectively) and control rats (25%, 25%, 33%, respectively), indicating that stimulation of cardiac β1AR induced cardioprotection. This response was prevented by pretreatment with AT and DPCPX, confirming the involvement of cardiac β1AR and A1R. Conclusion Pharmacological modulation of cardiac β1AR and A1R could be a potential therapeutic strategy to reduce severe arrhythmias and increase life expectancy in PD patients.
RESUMO
The aim of the present study was to investigate the effects of different periods of ovariectomy and 17â- estradiol replacement on apoptotic cell death and expression of members of the Bcl-2 family in the rat hippocampus. Hippocampi were obtained from rats in proestrus, ovariectomized (15 days, 21 days and 36 days), ovariectomized for 15 days and then treated with 17â-estradiol for 7 or 21 days, and rats ovariectomized and immediately treated with 17â-estradiol for 21 days. The expression of Bcl-2 and Bax and the number of apoptotic cells were determined. Ovariectomy decreased Bcl-2 expression and increased Bax expression and the number of apoptotic cells. Replacement with 17â-estradiol (21 days) throughout the post-ovariectomy period reduced the number of apoptotic cells to the control levels, and prevented the effects of ovariectomy on Baxexpression, but only partially restored the Bcl-2 expression. After 15 days of ovariectomy, the replacementwith 17â-estradiol for 21 days, but not for 7 days, restored the Bcl-2 and Bax expression and the percentageof apoptotic cells to the levels found in the proestrus control.The present results show that a physiological concentration of 17â-estradiol my help maintainlong-term neuronal viability by regulating the expression of members of the Bcl-2 family. Even after a period of hormonal deprivation, treatment with 17â-estradiol is able to restore the expression of Bax and Bcl-2 to control levels, but the duration of the treatment is a key factor to obtain the desired effect. These dataprovide new understanding into the mechanisms contributing to the neuroprotective action of estrogen.
