RESUMO
Pharmacological concentrations of melatonin reduce reperfusion arrhythmias, but less is known about the antiarrhythmic protection of the physiological circadian rhythm of melatonin. Bilateral surgical removal of the superior cervical ganglia irreversibly suppresses melatonin rhythmicity. This study aimed to analyze the cardiac electrophysiological effects of the loss of melatonin circadian oscillation and the role played by myocardial melatonin membrane receptors, SERCA2A, TNFα, nitrotyrosine, TGFß, KATP channels, and connexin 43. Three weeks after bilateral removal of the superior cervical ganglia or sham surgery, the hearts were isolated and submitted to ten minutes of regional ischemia followed by ten minutes of reperfusion. Arrhythmias, mainly ventricular tachycardia, increased during reperfusion in the ganglionectomy group. These hearts also suffered an epicardial electrical activation delay that increased during ischemia, action potential alternants, triggered activity, and dispersion of action potential duration. Hearts from ganglionectomized rats showed a reduction of the cardioprotective MT2 receptors, the MT1 receptors, and SERCA2A. Markers of nitroxidative stress (nitrotyrosine), inflammation (TNFα), and fibrosis (TGFß and vimentin) did not change between groups. Connexin 43 lateralization and the pore-forming subunit (Kir6.1) of KATP channels increased in the experimental group. We conclude that the loss of the circadian rhythm of melatonin predisposes the heart to suffer cardiac arrhythmias, mainly ventricular tachycardia, due to conduction disorders and changes in repolarization.
Assuntos
Arritmias Cardíacas/patologia , Ganglionectomia/efeitos adversos , Coração/fisiopatologia , Traumatismo por Reperfusão Miocárdica/cirurgia , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/metabolismo , Ritmo Circadiano , Conexina 43/genética , Conexina 43/metabolismo , Masculino , Melatonina/metabolismo , Ratos , Ratos Wistar , Receptores de Melatonina/genética , Receptores de Melatonina/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismoRESUMO
1,8-Cineole is a terpenoid present in many essential oil of plants with several pharmacological and biological effects, including antinociceptive, smooth muscle relaxant and ion channel activation. Also, 1,8-cineole blocked action potentials, reducing excitability of peripheral neurons. The objective of this work was to investigate effects of 1,8-cineole on Na(+) currents (INa(+)) in dissociated superior cervical ganglion neurons (SCG). Wistar rats of both sexes were used (10-12 weeks old, 200-300g). SCG's were dissected and neurons were enzymatically treated. To study 1,8-cineole effect on INa(+), the patch-clamp technique in whole-cell mode was employed. 1,8-Cineole (6.0mM) partially blocked INa(+) in SCG neurons. The effect stabilized within â¼150s and there was a partial recovery of INa(+) after washout. Current density was reduced from -105.8 to -83.7pA/pF, corresponding to a decrease to â¼20% of control. 1,8-Cineole also reduced the time-to-peak of INa(+) activation and the amplitude and decay time constants of INa(+) inactivation. Current-voltage plots revealed that 1,8-cineole left-shifted the V1/2 of both activation and inactivation curves by â¼10 and â¼20mV, respectively. In conclusion, we demonstrate that 1,8-cineole directly affects Na(+) channels of the SCG by modifying several gating parameters that are likely to be the major cause of excitability blockade.
Assuntos
Cicloexanóis/farmacologia , Monoterpenos/farmacologia , Neurônios/efeitos dos fármacos , Bloqueadores dos Canais de Sódio/farmacologia , Canais de Sódio/fisiologia , Gânglio Cervical Superior/efeitos dos fármacos , Animais , Eucaliptol , Feminino , Ativação do Canal Iônico/efeitos dos fármacos , Masculino , Neurônios/fisiologia , Ratos Wistar , Gânglio Cervical Superior/citologia , Gânglio Cervical Superior/fisiologiaRESUMO
The participation of sympathetic nerve fibers in the innervation of the nasal-associated lymphoid tissues (NALT) was investigated in hamsters. Vesicular monoamine transporter 2 (VMAT2), an established sympathetic marker, is expressed in all neurons of superior cervical ganglia (SCG). In addition, VMAT2 -immunoreactive nerve fibers were localized in the NALT as well as in adjacent anatomical structures of the upper respiratory tract. Unilateral surgical ablation of the SCG abolished VMAT2 innervation patterns ipsilaterally while the contra lateral side is unaffected. These results provide the anatomical substrate for a neuroimmune connection in the NALT.