SPECTRAL-ANALYSIS OF HEMODYNAMICS DURING INFUSIONS OF EPINEPHRINE AND NOREPINEPHRINE IN MEN

Spectral analysis of fluctuations in heart rate (HR) and arterial blood pressure (BP) during a 6-h infusion of epinephrine (15 ng.kg(-1).min(-1)) or norepinephrine (30 ng.kg(-1).min(-1)) in 10 normotensive males was used to analyze effects of peripheral sympathetic nervous system activity and adrenal medullary discharge on cardiovascular variability. Power spectra were calculated for each 5-min period for HR, systolic BP, and diastolic BP to yield power values for three frequency bands: low (0.02-0.06 Hz), mid (0.07-0.14 Hz), and high (0.15-0.40 Hz). Infusion of epinephrine and norepinephrine induced plasma concentrations of epinephrine and norepinephrine, respectively, within the high physiological range. Spectral analysis showed that low-frequency fluctuations of BP during infusions of epinephrine and midfrequency fluctuations of BP during infusion of norepinephrine changed in opposite directions. These fluctuations may represent different components of short-term cardiovascular control mechanisms during situations that mimic increased sympathoadrenal activity. No changes were observed in HR fluctuations or high-frequency fluctuations of BP after either catecholamine. Our data imply that changes in concentrations of circulating catecholamines cannot be unequivocally labeled as indexes of an altered sympathoadrenal involvement in short-term cardiovascular control

Augmented levels of macrophage and Th1 cell-related cytokine mRNA in submandibular glands of MRL/lpr mice with autoimmune sialoadenitis

MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop destructive inflammation of the salivary and lachrymal glands resembling Sjögren's syndrome (SS), representing an animal model to study this disease. We used in situ hybridization with synthetic radiolabelled oligonucleotide probes to examine expression of mRNA encoding pro- and anti-inflammatory cytokines in submandibular glands of 2, 3, 4 and 5-month-old MRL/lpr mice. Phenotypic composition of submandibular gland infiltrates was evaluated by immunohistochemistry. Cells expressing tumour necrosis factor-alpha (TNF-α), IL-1β, IL-6 and IL-12 mRNA were strongly up-regulated at about the time of onset of sialoadenitis, suggesting a role of these cytokines in development of the disease. Interferon-gamma (IFN-γ) and cytolysin mRNA-expressing cells were gradually up-regulated over the disease course up to 5 months of age, the time when sialoadenitis is at its height, favouring a role of these cytokines in progression of the disease as well. Low levels of IL-10 and transforming growth factor-beta (TGF-β) mRNA-expressing cells were observed at 2, 3 and 4 months of age, and were almost undetectable at 5 months. Maximum levels of CD4+, CD8+ and interdigitating/dendritic cells, as well as of MHC class II and MHC class I expression were seen at 3 months, with CD4+ outnumbering CD8+ cells. Maximum levels of macrophages were seen at 4 months of age. These data argue for a major role of the proinflammatory cytokines TNF-α, IL-1β, IL-6, IL-12, IFN-γ and cytolysin in initiation and perpetuation of autoimmune sialoadenitis in MRL/lpr mice, probably in conjunction with an insufficiency of the anti-inflammatory cytokines TGF-β and IL-10