Modification of the rat aortic wall during ageing; possible relation with decrease of peptidergic innervation.

Structural changes of the male rat aorta were followed from birth to old age in male and female rats. In males, the vessel media width and area progressively increase concomitantly with a decrease of nuclei density during ageing, suggesting an hypertrophy of the smooth muscle cells. These correlations were however not evidenced in females. TUNEL-positive cells were found in media of 4 and 6 months in both sexes, mainly on the luminal side and in the adventitia. When biochemical markers were investigated with immunohistochemistry, media was uniformly stained by the anti-vimentin and anti-alpha-smooth actin at all stages investigated. On the contrary, the surface of media stained with anti-desmin decreased during ageing, especially on the luminal side. As observed with electron microscopy, with ageing the endothelium is replaced by small cells with pseudopodia adhering to the vestigial elastic lamina and infiltrating into the extracellular matrix left after the disappearance of smooth muscle cells. In addition, in the older rats (25-29 months) the elastic laminae are completely disorganised. Hypertrophy of the smooth muscle cells was confirmed by this approach. In parallel to this study, perivascular peptidergic innervation was stained with antibodies against calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) at different ages during the whole life of rats. These peptides are present in stages younger than 6 months, then gradually disappear. In one year animals and older, the peptidergic innervation has totally disappeared. We discuss the possible role of peptidergic innervation in the control of the vessel wall cellular stability during ageing.

Rat lung alveolar type II cell line maintains sodium transport characteristics of primary culture.

Culture of primary alveolar type II cells has been widely used to investigate the Na+ transport characteristics of alveolar epithelium. However, this model was restricted by early morphological and physiological dedifferentiation in culture. Recently, a cell line has been obtained by transfection of neonatal type II cells with the simian virus SV40 large T antigen gene (SV40-T2). SV40-T2 cells have retained proliferative characteristics of the primary type II cells (Clement et al., 1991, Exp. Cell Res., 196:198-205.) In the present study, we have characterized Na+ transport pathways in SV40-T2 cells. SV40-T2 cells retained most cardinal properties of the original alveolar epithelial cells. Na+ entry occurred, as in primary cultures, through both Na(+)-cotransporters and amiloride-sensitive Na+ channels. SV40-T2 cells expressed Na(+)-phosphate. Na(+)-amino acid and Na(+)-K(+)-Cl cotransports which are quantitatively similar to that of primary cultures. The existence of amiloride-sensitive Na+ channels was supported by molecular and functional data. SV40-T2 expressed the cloned alpha- and gamma-mRNAs for the rat epithelial Na+ channel (rENaC), whereas beta subunit was not detected, and 22Na+ influx was significantly inhibited by 10 microM amiloride. Na+, which enters SV40-T2 cells, is extruded through a Na+, K(+)-ATPase: mRNA for alpha 1 and beta 1 isoforms of Na+, K(+)-ATPase were present and Na+, K(+)-ATPase activity was evidenced either on intact cells by the presence of a ouabain-sensitive component of 86Rb+ influx or on cell homogenates by the measurement of ouabain-inhibitable ATP hydrolysis. These results indicate that SV40-T2 cell line displays most of the Na+ transport characteristics of well-differentiated primary cells in the first days of culture. We conclude that the SV40-T2 cell line provides a model of differentiated alveolar type II cells and may be a powerful tool to study, in vitro, the modulation of Na+ transport in pathophysiological conditions.

Left ventricular function during weaning of patients with chronic obstructive pulmonary disease.

OBJECTIVE: Determine the evolution of left ventricular ejection fraction during weaning. DESIGN: Prospective study. SETTING: Intensive care unit of a university teaching hospital. PATIENTS AND PARTICIPANTS: 12 consecutive mechanically ventilated patients, without documented coronary artery disease, suffering from acute exacerbation of chronic obstructive pulmonary disease and able to be weaned. MEASUREMENTS AND RESULTS: Left ventricular ejection fraction was determined during mechanical ventilation, inspiratory pressure support (10 cmH2O) and spontaneous ventilation with constant inspiratory oxygen fraction using technetium 99m radionuclide angiography. Spontaneous ventilation induced a significant decrease in left ventricular ejection fraction from 54.5 +/- 12.4 to 47.0 +/- 13% (p < 0.01). Inspiratory pressure support induced a slight but non-significant decrease in left ventricular ejection fraction from 55.0 +/- 12.1 to 50.3 +/- 12.4%. Left ventricular ejection fraction was homogeneously reduced by spontaneous ventilation without patent regional wall motion abnormalities of the left ventricle. Myocardial 201thallium imaging performed 15 min after weaning showed a normal perfusion in the left ventricle anterior and posterior free wall. CONCLUSION: Weaning of patients suffering from chronic obstructive pulmonary disease without coronary artery disease induced a significant reduction in left ventricular ejection fraction. The non significant decrease in left ventricular ejection fraction observed with inspiratory pressure support suggested that our results might be explained by a weaning induced increase in afterload.