BackgroundIntake of ethanol (alcohol) has been shown to influence cardiovascular function; the underlying brain mechanism remains unclear. Noting that nitric oxide (NO) system in the CNS is involved in the regulation of cardiovascular function, the present study examined the role of NO in medulla in ethanol-induced cardiovascular changes.MethodsEthanol was administered by oral gavage at dose of 3.2 g/kg once every day for 8 consecutive days. Changes in blood pressure (BP) and heart rate (HR) in response to ethanol were measured by radiotelemetry method in freely moving female Sprague-Dawley rats. NO modulators were applied by intracerebroventricular (ICV) injection. The protein levels of nitric oxide synthase (NOS) and NO content in rostroventral medulla were measured by Western blot and nitrate/nitrite colorimetric assay kit, respectively.ResultsEthanol intake had little effects on basal BP and HR following 8 consecutive day treatments. A significant increase in HR but not BP following ethanol intake was observed at 6th and 8th, but not at 1st and 4th day treatments as compared with saline group. A decrease in the protein expression of neuronal NOS (nNOS) but not inducible NOS or endothelial NOS and a decline in the level of NO in the medulla 30 min after ethanol administration was observed at 8th day treatment. ICV treatment with NO donors attenuated ethanol-induced tachycardia effects at 8th day treatment. Ethanol produced significantly tachycardia responses when ICV nNOS inhibitors were given at 1st day treatment.ConclusionOur results suggest that medulla nNOS/NO pathways play an important role in ethanol regulation of HR.

Our results indicate that EtOH augmentation of glutamatergic NMDA receptors/NO/GABA pathways in the RVLM may participate in the hypotensive effects induced by acute administration of EtOH.

The abnormal accumulation of amyloid-␤ peptides (A␤) is one of the main characteristics of Alzheimer's disease (AD). Cerebro-and cardiovascular diseases may be the risk factors for developing AD. The effect of A␤ on central sympathetic control of cardiovascular function remains unclear. The present study examines the acute effects of A␤ oligomers on the function of NMDA receptors, a subtype of ionotropic glutamate receptors, in rat sympathetic preganglionic neurons (SPNs). In the in vitro electrophysiological study, A␤ 1-40 but not A␤ 1-42 applied by superfusion for 5 min significantly potentiated NMDA-induced depolarizations in SPNs of neonatal rat spinal cord slice preparation. Application of A␤ 1-40 had little effects on AMPA-induced depolarizations or GABA-induced hyperpolarizations. Treatment with a selective protein kinase C (PKC) inhibitor applied together with A␤ 1-40 blocked the augmentation by A␤ 1-40 of NMDA-induced depolarizations. Western blot analysis showed an increase in the levels of phosphoserine 896, selectively regulated by PKC, without significant changes in phosphoserine 897 on GluN1 subunits in lateral horn areas of spinal cord slices following treatment with A␤ 1-40 .In the in vivo study, intrathecal injection of A␤ 1-40 (0.2 nmol) potentiated the pressor effects induced by NMDA (2 nmol) injected intrathecally in urethane-anesthetized rats. These results suggest that different fragments of A␤ may have differential effects on the NMDA receptor function and the selective augmentation of NMDA receptor function by A␤ 1-40 may involve PKC-dependent mechanisms in sympathetic preganglionic neurons.

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