Reduced neural baroreflex sensitivity is related to enhanced endothelial function in patients with end-stage liver disease

Objectives: Reduced baroreflex sensitivity (BRS) is a frequent complication in end-stage liver disease, but the underlying mechanism is unknown. We investigated the mechanical and neural components of BRS. Increased nitric oxide (NO) production has been reported in end-stage liver failure. Based on earlier experiments, we hypothesised that enhanced endothelial function might affect baroreflex function. Therefore, we explored the relation between endothelial function and the components of BRS.Materials and methods: We enrolled 24 patients and 23 controls. BRS was determined by the spontaneous sequence method. Mechanical component was characterised by the distensibility coefficient (DC) of common carotid artery. Neural component was estimated as the ratio of integrated BRS and DC. Endothelial function was quantified by flow-mediated dilation (FMD) of the brachial artery.Results: Integrated BRS was reduced in patients [7.00 (5.80-9.25) vs. 11.1 (8.50-14.80) ms/mmHg]. The mechanical component was not different in the two groups, whereas neural component showed significant reduction in patients (3.541.20 vs. 4.48 +/- 1.43ms/10(-3)). FMD was higher in patients (9.81 +/- 3.77 vs. 5.59 +/- 1.36%). FMD and neural BRS were directly related in controls (r=0.62), but inversely related in patients (r=-0.49).Conclusions: Baroreflex impairment in end-stage liver disease might be explained by deterioration of the neural component, while the mechanical component appears to be preserved. Endothelial NO may enhance BRS in health; however, central endothelial overproduction of NO likely contributes to the reduction of neural component of BRS in patients awaiting liver transplantation

Immunohistochemical properties of the peripheral neurons projecting to the pig bulbospongiosus muscle.

Retrograde neuronal tracing and single labelling immunofluorescence methods were used to define the neurochemical content of the peripheral autonomic and sensitive neurons projecting to the male pig striated bulbospongiosus muscle (BSM). The retrograde fluorescent neuronal tracer Fast Blue (FB) was injected into the left bulbospongiosus muscle of four intact impuberal pigs. After a 10-day survival time, the ipsilateral sacral sympathetic trunk ganglia (STGs), the caudal mesenteric ganglion (CMG), and the sacral spinal ganglia (SGs) were collected from each animal. In FB1 neurons of these ganglia, the presence of cathecolamine- (tyrosine hydroxylase-TH), acetylcholine- (vesicular acetylcholine transporter- VChAT), or nitric oxide-synthesizing (neuronal Nitric Oxide Synthase- nNOS) enzymes and of some biologically active peptides (calcitonine gene-related peptide-CGRP, Leu-Enkephaline-LENK, Neuropeptide Y-NPY, Substance P-SP and Vasoactive Intestinal Peptide-VIP) were studied. The ipsilateral STGs FB1 neurons showed immunoreactivity principally for TH and NPY and in decreasing order for VIP, VChAT, SP, CGRP, nNOS, and LENK. The left CMG FB1 neurons were immunoreactive to TH and NPY, and in smaller proportions for VIP, LENK, VChAT, CGRP, nNOS, and SP. The ipsilateral SGs FB1 neurons resulted immunoractive for CGRP, LENK, NPY, nNOS, SP, and VChAT. The heterogeneous neurochemical content of the peripheral neurons projecting to the pig BSM allows us to hypothesize the involvement of autonomic ganglia in the activity of both blood vessels and striated fibers of the muscle and the involvement of sensory ganglia in the afferent transmission from the muscle to spinal cord and in antidromic mechanisms that causes the relaxation of the BSM blood vessels