Nitric oxide (NO) plays a crucial role not only in regulation of blood pressure but also in maintenance of cardiac autonomic tone and its deficiency induced hypertension is accompanied by cardiac autonomic dysfunction. However, underlying mechanisms are not clearly defined. We hypothesized that sympathetic activation mediates hemodynamic and cardiac autonomic changes consequent to deficient NO synthesis. We used chemical sympathectomy by 6-hydroxydopamine to examine the influence of sympathetic innervation on baroreflex sensitivity (BRS) and heart rate variability (HRV) of chronic NG-nitro-L-arginine methyl ester (L-NAME) treated adult Wistar rats. BRS was determined from heart rate responses to changes in systolic arterial pressure achieved by intravenous administration of phenylephrine and sodium nitroprusside. Time and frequency domain measures of HRV were calculated from 5-min electrocardiogram recordings. Chronic L-NAME administration (50 mg/kg per day for 7 days orally through gavage) in control rats produced significant elevation of blood pressure, tachycardia, attenuation of BRS for bradycardia and tachycardia reflex and fall in time as well as frequency domain parameters of HRV. Sympathectomy completely abolished the pressor as well as tachycardic effect of chronic L-NAME. In addition, BRS and HRV improved after removal of sympathetic influence in chronic L-NAME treated rats. These results support the concept that an exaggerated sympathetic activity is the principal mechanism of chronic L-NAME hypertension and associated autonomic dysfunction., M. Chaswal, S. Das, J. Prasad, A. Katyal, M. Fahim., and Obsahuje bibliografii
The experimental evidence for the antipyretic action of arginine vasopressin (AVP) in guinea-pigs can be summarized as follows: The febrile response to a bacterial pyrogen can be reduced by a microinfusions of exogenous AVP into the ventral septal area of the limbic system. Immunohistochemical studies indicate increased activity of AVP terminals in the ventral septal area (VSA) and in parvocellular AVP neurones of the hypothalamic paraventricular nucleus (PVN) in several stressful situations accompanied by reduced febrile responses (late stage of pregnancy, immobilization, cold adaptation, osmotic stimulation). Also the peripheral and/or central release of AVP measured in some of these situations is increased. Electrical stimulation of the PVN suppresses fever, this suppression can, at least partly, be cancelled by simultaneous intraseptal application of the vasopressinergic VI receptor antagonist. The documented AVP pathways from the PVN to the septum receive noradrenergic afferents from the lower brainstem. Chronic destruction of these afferents by microinjections of 6-hydroxydopamine (6-OHDA) significantly reduced the fever responses to pyrogen application, while microinfusion of noradrenaline (NA) enhances the fever reaction.
Parkinson's disease (PD) is a neurodegenerative disease with
a progressive loss of mesencephalic dopaminergic neurons of the
substantia nigra (SN). To further evaluate its pathophysiology,
accurate animal models are needed. The current study aims to
verify the impact of a 6-hydroxydopamine (6-OHDA) bilateral
microinjection into the SN on gastrointestinal symptoms in rats
and confirm that the 6-OHDA rat model is an appropriate tool to
investigate the mechanisms of Parkinsonian GI disorders.
Immunohistochemistry, digital X-ray imaging, short-circuit
current, FITC-dextran permeability and ultra-performance liquid
chromatography tandem mass spectrometry were used in this
study. The results indicated that the dopaminergic neurons in SN
and fibres in the striatum were markedly reduced in 6-OHDA
rats. The 6-OHDA rats manifested reductions in occupancy in
a rotarod test and increases in daily food debris but no difference
in body mass or daily consumption. Compared with control rats,
faecal pellets and their contents were significantly decreased,
whereas gastric emptying and intestinal transport were delayed
in 6-OHDA rats. The increased in vivo FITC-dextran permeability
and decreased intestinal transepithelial resistance in the model
suggest attenuated barrier function in the digestive tract in the
PD model. Moreover, inflammatory factors in the plasma showed
that pro-inflammatory factors IL-1β and IL-8 were significantly
increased in 6-OHDA rats. Collectively, these findings indicate
that the model is an interesting experimental tool to investigate
the mechanisms involved in the progression of gastrointestinal
dysfunction in PD.