PubMed Health⌕ Search

Biomedical subjects

J P Besombes

Publications and source records attributed to J P Besombes.

At least 19 recordsLinked to original sources
PubMed1999

Estradiol increases rat aorta endothelium-derived relaxing factor (EDRF) activity without changes in endothelial NO synthase gene expression: possible role of decreased endothelium-derived superoxide anion production.

OBJECTIVES: Estradiol is known to exert a protective effect against atherosclerosis, but the mechanism(s) whereby this protection is mediated is/are unclear. However, estradiol-treated castrated animals exhibit increased activity of endothelium-derived relaxing factor (EDRF), which could contribute to vasculoprotection. In the present work, we investigated the molecular mechanism(s) of the enhancement of EDRF activity in the thoracic aorta of oophorectomized female rats given 17 beta-estradiol (E2, 2 or 40 micrograms/kg/day) compared to those given a placebo. METHODS AND RESULTS: The abundance in the thoracic aorta of NO synthase I, II and III mRNA (using RT-PCR) and of NO synthase I, II and III immunoreactive protein (using Western blotting) was unaltered by E2. NO synthase activity (based on arginine/citrulline conversion) in thoracic aorta homogenates did not differ significantly among the three groups, suggesting that NO production was not enhanced by E2. In contrast, lucigenin-enhanced chemiluminescence of aorta from the E2 group was decreased compared to that of the placebo group. Desendothelialization and exogenously added superoxide dismutase suggested that this difference was due to a decrease in extracellular endothelium-derived production of superoxide anion (O2-.). Experiments in cultured bovine aortic endothelial cells confirmed a decreased extracellular production of O2-. in response to ethinylestradiol (1 nM) using both lucigenin-enhanced chemiluminescence and ESR spectroscopy. Luminol-enhanced chemiluminescence revealed that ethinylestradioltreated cultured endothelial cells generated less peroxynitrite (the byproduct of NO-. and O2-. interaction) than control cells. CONCLUSION: Estradiol increases rat aorta EDRF activity in the absence of changes in endothelial NO synthase gene expression. The decreased endothelium-derived generation of O2-. in response to estrogens could account for enhanced EDRF-NO bioactivity and decreased peroxynitrite release. All of these effects could contribute to the vascular protective properties of estrogens.

Animals↗
PubMed1998

Nasal nitric oxide concentration is decreased in heart failure patients receiving nitrates.

Nitric oxide (NO) is a free radical gas and a short-lived messenger which has many paracrine functions. Direct assessment of NO production is very difficult in vivo. However, the paranasal cavities generate a high amount of NO which diffuses in the nasal cavity where it can be easily measured. Several studies have suggested alterations of the NO production in heart failure. Thus, we assessed nasal NO concentration in normal subjects and in heart failure patients. The nasal NO concentration averaged 227 +/- 10 ppb in the control group (n = 20), and 210 +/- 10, 198 +/- 20 and 159 +/- 54 ppb in New York Heart Association (NYHA) class II (n = 30), III (n = 28) and IV (n = 7) patients, respectively (mean +/- standard error [SE], not significant using analysis of variance [ANOVA]). Nasal NO level was not influenced by age, sex or etiology of the heart failure or by treatment with frusemide, angiotensin-converting enzyme inhibitor or digoxin. However, treatment with NO-releasing drugs (nitrates or molsidomine) significantly decreased the nasal NO level in heart failure patients. A two-way ANOVA revealed that treatment with a NO-releasing drug influenced nasal NO concentration (P = 0.0005), whereas NYHA class did not (P = 0.23), with a trend towards an interaction between the two parameters (P = 0.09): the inhibitory effect of NO-releasing drug on nasal NO concentration was more pronounced in severe heart failure. In an additional group of 12 patients (NYHA class II or III), the nasal NO concentration was 174 +/- 19 ppb during NO-releasing drug treatment and increased to 231 +/- 27 ppb 3 days after withdrawal of the nitrates (P = 0.0007 using paired t-test). Conversely, the nasal NO concentration in another group of seven patients (NYHA class II or III) was 219 +/- 32 ppb without nitrate treatment and decreased to 188 +/- 28 ppb 7 days after nitrate addition (P = 0.02 using paired t-test). In contrast, the nasal NO concentration in another group of ten ischemic patients without heart failure was 203 +/- 25 ppb without nitrate treatment and was similar (207 +/- 28 ppb) 7 days after nitrate addition (not significant using paired t-test). In conclusion, nasal NO production is normal in heart failure, except in patients receiving NO-releasing drugs. Nasal NO concentration could be useful for investigating the mechanism(s) by which exogenous NO donors decrease endogenous NO production.

Adult↗
PubMed1997

Nasal nitric oxide is increased in allergic rhinitis.

BACKGROUND: Nitric oxide (NO) plays a major role in the regulation of vascular tone and in non-specific host defence. The epithelium in the paranasal sinuses was recently identified as the major site of NO production in the upper airways. OBJECTIVE: To investigate NO status in allergic rhinitis, we compared the NO concentration in the nasal cavities of control subjects (n = 19) and in patients with allergic rhinitis (n = 36) with symptoms (WS, n = 17) or without symptoms (WOS, n = 19) on the day of the test. METHODS: NO concentration was measured using a chemiluminescent analyser aspiring from each nasal cavity at a sampling flow rate of 0.7 L/min, before and 10 min after administration of a nasal vasoconstrictor. RESULTS: The mean NO concentration (+/- SE) in the control was 235 +/- 11 ppb and 225 +/- 9 ppb in the right and left nostrils respectively, and was decreased by 14% and 12% by the nasal vasoconstrictor (P < 0.001). The NO concentration in patients with allergic rhinitis was significantly higher in the right and left nostrils (382 +/- 20 ppb and 396 +/- 28 respectively, P < 0.0001 versus control). All WOS patients demonstrated normal or increased NO concentrations in both nostrils, whereas two WS patients showed decreased NO concentrations in the left nostril. Inhalation of a nasal vasoconstrictor increased NO concentration by 6% and 27% in the right and left nostrils respectively in WS patients. CONCLUSION: Nasal NO concentration is increased in patients with allergic rhinitis. Interestingly, patients without symptoms on the day of the test also showed a clear-cut increase in nasal NO production, which could reflect a permanent inflammation of the sinus mucosa.

Adult↗
PubMed1996

Nitric oxide and superoxide anion production during endothelial cell proliferation.

We have previously reported that nitric oxide (NO) synthase activity, protein, and mRNA are increased in proliferating compared with postconfluent bovine aortic endothelial cells (BAEC). Because superoxide anion inactivates NO, in the present study, we have assessed the effect of proliferation on superoxide anion production by use of cytochrome c reduction. The superoxide anion production in proliferating cells was increased about threefold compared with postconfluent cells in both basal and calcium ionophore-stimulated conditions and exceeded the amount of released nitrite and nitrate (NOx) in all cases. A-23187 (1 microM) stimulated the superoxide anion production about twofold at all stages of confluence. Because superoxide anion can inactivate NO, we then assessed the effect of proliferation on NO bioactivity released in the conditioned medium, by use of RFL-6 cells (reporter cells very rich in guanylate cyclase, which on activation by NO generates guanosine 3',5'-cyclic monophosphate, second messenger of NO). In the absence of added superoxide dismutase (SOD) in the conditioned medium, the guanylate cyclase-stimulating activities evoked by A-23187 from proliferating and growth-arrested cells were similar, despite a greater NOx release in the former. When SOD (100 U/ml) was added in the conditioned medium, the guanylate cyclase-stimulating activity evoked by 1 microM A-23187 was increased approximately 10-fold and closely paralleled NOx release (i.e., was greater in supernatant of proliferating cells than in that of growth-arrested cells). Thus BAEC release more superoxide anion extracellularly than NO at all stages of confluence. Endothelium-derived superoxide anion is a major determinant of the breakdown of NO.

Animals↗
PubMed1994

Arachidonic acid metabolism in alveolar macrophages from actively sensitized guinea-pigs: effects of sensitization and specific allergen.

Arachidonic acid (AA) metabolism, including mediator release and lipid turnover, was explored in [3H]AA-radiolabelled alveolar macrophages obtained from guinea-pigs actively sensitized to ovalbumin (sAM) and controls (cAM). The basal and allergen-induced AA metabolism of cAM and sAM were examined in the presence and absence of homologous serum obtained from the same control or sensitized animals. Basal AA metabolism of cAM and sAM involved the release of lipoxygenase and cyclooxygenase [3H]metabolites and free [3H]AA into the culture medium. However, in sAM, the production of free [3H]AA was significantly lower than in cAM. The allergen had no effect on the basal AA metabolism of cAM and sAM or on the metabolism of cAM and sAM cultured in the presence of control serum. In contrast, it increased the [3H]LTC4-D4 and free [3H]AA production of sAM cultured with sensitized serum but not those of cAM cultured with the same sensitized serum. In sAM, the allergen effect disappeared when the sensitized serum was heated for 1 h to 56 degrees C. Our results suggest that two factors, both induced by the active sensitization of guinea-pigs, one in the serum and one on the macrophages obtained from sensitized guinea-pigs, are required for the allergen to have an impact on the AA metabolism of alveolar macrophages in increasing the production of 5-lipoxygenase metabolites.

Allergens↗
PubMed1994

Fatty-acid synthase activity and mRNA level in hypertrophic type II cells from silica-treated rats.

Silica instillation causes a massive increase in lung surfactant. Two populations of type II pneumocytes can be isolated from rats administered silica by intratracheal injection: type IIA cells similar to type II cells from normal rats and type IIB cells, which are larger and contain elevated levels of surfactant protein A and phospholipid. Activities of choline-phosphate cytidylyltransferase, a rate-regulatory enzyme in phosphatidylcholine biosynthesis, and fatty-acid synthase (FAS) are increased in type IIB cells isolated from rats 14 days after silica injection. In the present study, we examined the increase in FAS and cytidylyltransferase activities in type IIB cells as a function of time after silica administration. FAS activity increased rapidly, was approximately threefold elevated 1 day after silica administration and has reached close to the maximum increase by 3 days. Cytidylyltransferase activity was not increased on day 1, was significantly increased on day 3 but was not maximally increased until day 7. Inhibition of de novo fatty-acid biosynthesis, by in vivo injection of hydroxycitric acid and inclusion of agaric acid in the type II cell culture medium, abolished the increase in cytidylyltransferase activity on day 3 but not FAS and had no effect on activities of two other enzymes of phospholipid synthesis. FAS mRNA levels were not increased in type IIB cells isolated 1-14 days after silica injection. These data show that the increase in FAS activity in type IIB cells is an early response to silica, that it mediates the increase in cytidylyltransferase activity, and that it is not due to enhanced FAS gene expression.

Animals↗
PubMed1992

[Respiratory function in heroin addicts with or without HIV infection. Study of 107 cases with a 6-month follow-up of 36 subjects].

Both intravenous drug addiction (IVDA) and HIV infection can involve respiratory system. So, we have studied pulmonary function in 107 heroin abusers during deprivation to clarify the extent of these two factors respectively. Two groups were separated: 50 subjects without HIV infection (HIV-) and 57 seropositive subjects (HIV+) in early stage of the disease (mean CD4 lymphocytes: 457 +/- 61/mm3). 36 subjects have been investigated 6 months later to evaluate the reversibility of possible observed abnormalities. Altered pulmonary function was encountered similarly in HIV+ and HIV-. DLco was abnormal in 40% of cases both in HIV+ (mean DLco: 63.4 +/- 1.1% of predicted values) and HIV- (mean DLco: 65.4 +/- 1.5% pred); obstructive lung disease was present in 18% of HIV- (FEV1/VC: 63.8 +/- 2.5) and 9% of HIV+ (FEV1/VC: 61 +/- 3.6); restrictive lung disease was found more frequently (16% vs 10%) in HIV+ (FEV1/VC: 81.2 +/- 2.1, TLC: 72.4 +/- 3.6% pred) than in HIV- (FEV1/VC: 84.2 +/- 1.6, TLC: 71.2 +/- 0.9% pred). These abnormalities were not associated with significant arterial blood gas modifications. As a whole, DLco tend to improve in the two groups and this significantly for HIV+ (p less than 0.03). But for individuals initial DLco alteration was persistent in 68% of cases suggesting slow improvement. In conclusion, in this study HIV+ and HIV- IVDA were not different concerning pulmonary function. In this risk group, DLco itself had a poor specificity and only it follow-up may be of interest for pulmonary opportunistic infection screening.

Adult↗
PubMed1991

Hyperventilation does not increase alveolar surfactant phospholipids in the anesthetized rat.

Pulmonary distension elicits an increase of the surfactant secretion. Effects of hyperventilation on this same secretion are less precise since they were observed under particular experimental conditions. We report a study of the effects of hyperventilation on the phospholipid content of alveolar lining fluid in the rat. One hour's hyperventilation induced by addition of a dead space to the tracheal cannula of anesthetized rats did not affect the phospholipid content of broncho-alveolar lavage fluid collected in situ immediately after killing. Phospholipid content (4.82 +/- 1.39 mg.g-1 dry lung weight) did not differ significantly from that in anesthetized spontaneously breathing rats (4.00 +/- 1.09 mg.g-1 dry lung weight). Furthermore, phospholipid content was not found to increase in animals maintained at 37 degrees C for 20 min (4.43 +/- 1.30 mg.g-1 dry lung weight) or 60 min (3.55 +/- 0.88 mg.g-1 dry lung weight) after killing. In conclusion the constancy of phospholipid content can be due either to a normal secretion or to a hypersecretion with a concomitant removal.

Animals↗
PubMed1989

Alveolar phospholipids, hyperventilation and temperature of conservation of rat lungs.

Hyperventilation has been found to increase the phospholipid content of broncho-alveolar lavage fluids. Had the temperature of conservation of the lungs an influence? Two groups of rats were allowed to ventilate normally (NV), and two groups (HV) were induced to hyperventilate for 1 h by addition of a dead space. After sacrifice, the isolated lungs were kept for 25 min at 37 degrees C (NV37 and HV37), or 10 degrees C (NV10 and HV10), and then washed at the same temperatures. The phospholipid content of lavage fluid was only found to be increased in the HV37 group (P less than 0.05). Neither hyperventilation followed by conservation of lungs at 10 degrees C nor normal ventilation followed by conservation of lungs at 37 degrees C led to an increase in phospholipid content. It was the association of hyperventilation and conservation of lungs at 37 degrees C that led to the increase. In vivo hyperventilation is thought to lead to an equal increase in secretion and reabsorption of alveolar phospholipids, and conservation of the lungs at 37 degrees C was thought to lead to an imbalance between these two processes.

Animals↗
PubMed1984

[Effects of pneumogastric nerve stimulation and injection of a beta 2 stimulant (terbutaline) on the lipid composition of the alveolar lining fluid and on pulmonary compliance in the rat].

The effects of vagal stimulation and of terbutaline injection on lipidic composition of alveolar fluid and pulmonary compliance were studied. Three groups of rats were used: control, after right vagus nerve stimulation, after 0.2 mg terbutaline injection. The lungs of the rats were isolated. We studied pulmonary pressure-volume curves with air and we measured pulmonary compliance. We realised an alveolar lavage to obtain alveolar lipids. We observed: Vagus nerve stimulation and beta 2 agonist significantly increased fatty acids of total lipids respectively by 52.5% and 25.5% and phospholipids, respectively by 43.6% and 25.7%. beta 2 agonist did not change fatty acid composition of total lipids and phospholipids. Right vagus nerve stimulation increased the percentage of palmitic acid in phospholipids and decreased the percentage of saturated fatty acids and of palmitic acid in total lipids. Terbutaline injection induced more significant changes in pressure-volume curves and in pulmonary compliance than right vagus nerve stimulation. Our results suggest that both vagal stimulation and beta 2 agonists increase lipid release in alveolar lining, but only vagal stimulation modifies the composition of these lipids. These modifications could be, at least in part, correlated with the changes observed in the pressure-volume curves.

Animals↗
PubMed1975

[Effect of practolol on experimental hypertension in dogs].

In the dog, the intra-venous injection of practolol (1 to 3 mg/kg) reduces the hypertension provoked by vagotomy and sino-aortic nerves section, or by intra-venous administration of potassium cyanide. But practolol differs from propranolol ; he does not modify hypertension observed after electrical stimulation of central end of saphene, laryngeal superior, or vagus nerf.

Animals↗