Immunoregulation mediated by the sympathetic nervous system.

A postulated immunoregulatory role for the autonomous nervous system was explored utilizing several in vivo and in vitro approaches. Local surgical denervation of the spleen in rats and general chemical sympathectomy by 6-hydroxydopamine combined with adrenalectomy yielded a similar removal of restraint expressed as enhancement in the number of PFC in response to immunization. Noradrenaline and the synthetic α-agonist clonidine which are, respectively, natural and artificial effector molecules of the sympathetic nervous system each strongly suppressed the in vitro induced immune response of murine spleen cells to SRBC. Further, radiometric-enzymatic assay of noradrenaline in the splenic pulp revealed a decrease in the content of this neurotransmitter just preceding the exponential phase of the immune response to SRBC (Days 3 and 4) in this site. Taken together, these findings point to a dynamic immunoregulatory relationship between the immune and sympathetic nervous system.     

The endocrine function of the fat cell-regulation by the sympathetic nervous system.

The landmark discovery of leptin established beyond question the fact that adipose tissue is a crucial active regulator of body weight, an endocrine organ in its own right and part of a feedback circuit possessing both afferent and efferent loops. This is in addition to its more established roles as a receiver of incoming endocrine signals and modulator of circulating hormones such as sex steroids. Since this discovery, much has been learned about the role of leptin in the afferent loop of the hypothalamic regulation of body weight and indeed about some of the neuro-endocrine circuitry involved in the regulation of appetite and weight. Much less, however, is known about the efferent limb of the circuit, specifically relating to how the hypothalamus is able to influence adipocyte behaviour and how this link may itself be influenced by endocrine and paracrine signals, both acting on and emanating from adipocytes themselves, acting at multiple levels.This review will focus on the role of the sympathetic nervous system (SNS) and adreno-medullary system in relation to the regulation of adipose tissue physiology and endocrine function. The evidence in support of the hypothesis that the SNS is a crucial mediator of the efferent loop of this feedback circuit will be considered.     

Role of the sympathetic nervous system in the alcohol-guanabenz hemodynamic interaction.

The present study evaluated the contribution of the sympathetic nervous system to the adverse hemodynamic action of ethanol on hypotensive responses in conscious unrestrained spontaneously hypertensive rats. Ethanol caused a dose-related attenuation of the hypotensive effect of guanabenz. An equivalent hypotensive response to sodium nitroprusside was not influenced by ethanol, which indicates a potential specific interaction between ethanol and guanabenz. Alternatively, it is possible that a preexisting high sympathetic nervous system activity, which occurred during nitroprusside infusion, may mask a sympathoexcitatory action of ethanol. Further, ethanol (1 g/kg) failed to reverse the hypotensive effect of the ganglionic blocker hexamethonium. This suggests that a centrally mediated sympathoexcitatory action of ethanol is involved, at least partly, in the reversal of hypotension. In addition, the antagonistic interaction between ethanol and guanabenz seems to take place within the central nervous system and involves opposite effects on central sympathetic tone. Finally, changes in plasma catecholamines provide supportive evidence for the involvement of the sympathetic nervous system in this interaction. In a separate group of conscious spontaneously hypertensive rats, ethanol (1 g/kg) reversed the guanabenz-evoked decreases in blood pressure and plasma catecholamine levels. It is concluded that (i) ethanol adversely interacts with centrally acting antihypertensive drugs through a mechanism that involves a directionally opposite effect on sympathetic activity, and (ii) a sympathetically mediated pressor effect of ethanol is enhanced in the presence of an inhibited central sympathetic tone.     

Sildenafil acts on the central nervous system increasing sympathetic activity.

Sildenafil induces vasodilation and is used for treating erectile dysfunction. Although its influence on resting heart function appears to be minimal, recent studies suggest that sildenafil can increase sympathetic activity. We therefore tested whether sildenafil injected into the central nervous system alters the autonomic control of the cardiovascular system in conscious rats. The effect of sildenafil citrate injected into the lateral cerebral ventricle was evaluated in conscious rats by means of the recording of lumbar sympathetic nerve activity (LSNA), spectral analysis of systolic arterial pressure and heart rate variability, spontaneous baroreflex sensitivity, and baroreflex control of LSNA. Intracerebroventricular (ICV, 100 microg /5 microl) administration of sildenafil caused remarkable tachycardia without significant change in basal arterial pressure and was associated with a conspicuous increase (47 +/- 14%) in LSNA. Spectral analysis demonstrated that systolic arterial pressure oscillations in the low frequency (LF) range were increased (from 6.3 +/- 1.5 to 12.8 +/- 3.8 mmHg(2)), whereas the high frequency (HF) range was not affected by ICV administration of sildenafil. Sildenafil increased pulse interval oscillations at LF and decreased them at HF. The LF-HF ratio increased from 0.04 +/- 0.01 to 0.17 +/- 0.06. Spontaneous baroreflex sensitivity measured by the sequence method and the baroreflex relationship between mean arterial pressure and LSNA were not affected by ICV administration of sildenafil. In conclusion, sildenafil elicited an increase in sympathetic nerve activity that is not baroreflex mediated, suggesting that this drug is able to elicit an autonomic imbalance of central origin. This finding may have implications for understanding the cardiovascular outcomes associated with the clinical use of this drug.     

The sympathetic nervous system is involved in variant Creutzfeldt-Jakob disease

Prion epizoonoses spread from animals consumed by humans raise the question of which pathways lead to prion neuroinvasion after oral exposure of humans. Here we show that neurons of sympathetic ganglia of patients with variant Creutzfeldt-Jakob disease (vCJD) accumulate the abnormal isoform of the protein prion. This observation shows the involvement of the sympathetic nervous system in the pathogenesis of vCJD and suggests a role for GUT-associated sympathetic neurons in prion propagation in humans after oral contamination.