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Biomedical subjects

C Advenier

Publications and source records attributed to C Advenier.

At least 217 records · Page 12Linked to original sources
PubMed1980

Bronchopulmonary effects of dopamine in the guinea-pig.

The effects of dopamine (DA) were studied in vivo on the pulmonary airway resistance of the unanaesthetized guinea-pig, and in vitro, on the isolated trachea of the same animal. DA relaxes the isolated trachea previously contracted by ACh, but only at very high concentrations (10(-4) to 10(-3) M) and appears to be approximately 7000 times less active than isoprenaline (ISO). The relaxation caused by DA is: (1) diminished by pretreatment with cocaine or reserpine indicating an indirect effect linked to a release of endogenous catecholamines; (2) increased by phentolamine, suggesting a masked contracting alpha-adrenergic component; (3) completely abolished by propranolol through competitive antagonism. In vivo, DA reduces the increase in pulmonary airway resistance provoked by ACh. Its action, which is mainly beta-adrenergic, is, nevertheless, 1.4 x 10(5) times less than that of ISO. Thus, dopaminoreceptors do not seem to exist in the tracheobronchial smooth muscle of the guinea-pig. DA only has partial beta-adrenergic agonistic action at that site.

Airway Resistance↗
PubMed1979

The effects of metiamide and H1 receptor blocking agents on anaphylactic response in guinea-pigs.

The effects of metiamide and of four H1 receptor blocking agents (mepyramine, promethazine, clemastine and ketotifene) on anaphylactic reaction were studied in the guinea-pig. The H1 blockers conferred partial protection which shows that with the experimental protocol utilized (challenge injection with high doses of antigen), histamine plays a lesser role than other mediators released or synthesized. Metiamide (30.0 mg/kg i.v.) noticeably enhanced the increase in pulmonary resistance observed during anaphylactic reaction and reduced the protective effect of the H1 antagonists on this parameter and on histamine release. These effects might be explained by an inhibition - at least partial - of the negative feed-back mechanism through which histamine controls its own release, or by a specific action of metiamide in high doses. The transient tachycardia initially observed in anaphylactic shock is partly related to stimulation of cardiac H2 receptors by the histamine released, since it is suppressed by metiamide.

Airway Resistance↗
PubMed1978

The effects of pentobarbitone and urethane on pulmonary airway resistance in guinea-pigs and their interactions with drugs.

1 Propranolol increased pulmonary airway resistance (PAR) in the conscious guinea-pig, whereas atropine had no effect, suggesting the existence of a continual sympathetic bronchodilator tone. 2 The direct bronchoconstrictor effects of histamine, acetylcholine and 5-hydroxytryptamine were modified by autonomic reflexes: a bronchodilator one, abolished by propranolol, and a cholinergic bronchoconstrictor one, seen with histamine. 3 Pentobarbitone increased PAR, an effect which was reduced by propranolol but which was unaffected by atropine. The bronchoconstrictor effects of histamine, acetylcholine and 5-hydroxytryptamine were potentiated by pentobarbitone. 4 Pentobarbitone therefore appears to inhibit the adrenergic bronchodilator tone and to depress adrenergic reflexes, these being the preponderant autonomic influences in these experiments. 5 Like pentobarbitone, urethane increased PAR in the conscious guinea-pig and potentiated the bronchoconstrictor effects of the three amines. These actions are similarly attributed to a reduction in adrenergic influences.

Airway Resistance↗
PubMed1972

Comparative study of six -adrenoceptive antagonists on airway resistance and heart rate in the guinea-pig.

1. The effects of six beta-adrenoceptive antagonists [(+/-)-propranolol, (+)-propranolol, (+/-)-sotalol, (+/-)-practolol, (+/-)-pindolol and (+/-)-procinolol] were studied on airway resistance and heart rate in guinea-pigs and dose-response curves constructed.2. All beta-adrenoceptive antagonists decreased heart rate and increased airway resistance. A significant correlation was found between the increase in airway resistance and the degree of bradycardia induced by all drugs except practolol. The orders of activity of the six drugs in inducing significant variations of the two parameters were respectively, for airway resistance: (+/-)-procinolol>(+/-)-pindolol>(+/-)-propranolol>(+/-)-sotalol>(+)-propranolol>(+/-)-practolol, and for heart rate: (+/-)-pindolol>(+/-)-procinolol>(+/-)-propranolol>(+/-)-sotalol>(+)-propranolol>(+/-)-practolol.3. (+/-)-Sotalol, (+/-)-pindolol and (+/-)-procinolol-induced changes in airway resistance and heart rate reached plateau values, which were not modified by increasing the dose. Since sotalol and procinolol have only very weak partial agonist and cardiac depressant properties, it appears that these changes can mainly be accounted for by the suppression of sympathetic tone. It is probable that this is also the case with pindolol.4. On the other hand, (+/-)-propranolol and (+)-propranolol induced dose-related changes in airway resistance and heart rate. Thus, a direct and non-specific effect of both drugs on the bronchial muscle, similar to that observed on the heart appears to be implicated, together with sympathetic tone suppression in these variations.5. (+/-)-Practolol-induced effects on airway resistance and heart rate were different from those observed with the five other beta-adrenoceptive antagonists.

Acetanilides↗
PubMedDate not supplied

Isolation and purification of three glucuronides of antipyrine. Proposal for an original analytical method for quantitation of sulpho- and glucuroconjugated metabolites.

The determination of the concentrations of antipyrine metabolites in biological fluids is hampered by the difficulty in obtaining pure conjugated compounds to be used as standards. Most authors have proposed determination of total forms by high performance liquid chromatography (HPLC) after deconjugation of these metabolites using chemical or enzymatic hydrolysis. Up to now there is no satisfactory hydrolysis method for the study of all antipyrine metabolites. The situation is further complicated by the fact that the deconjugated metabolites are highly unstable whichever technique is being used. Because of the lack of stability of all these molecules it has been necessary to isolate the glucuroconjugated compounds from urine. We describe a method which allows us to obtain highly purified glucuroconjugated metabolites of antipyrine. Sulphoconjugated compounds have been synthesized previously. We are thus able to propose a chromatographic procedure which allows us to determine simultaneously all stable phase I and phase II metabolites of antipyrine in biological fluids without any step of extraction. This analytical technique allows us to study the activity of the different isoenzymes implicated in the metabolism of antipyrine.

Antipyrine↗
PubMedDate not supplied

Tachykinin receptor antagonists and cough.

Several potent and selective antagonists for tachykinin receptors are now available and appear as powerful tools to investigate the physiological and pathological roles of tachykinins and to identify the type of receptor involved in their effect. Indeed, a lot of studies have shown that tachykinin NK2 receptor antagonists (SR 48968, MEN 10627) are able to inhibit cough induced by citric acid, capsaicin or allergen challenge in the unanesthetized guinea-pig or mechanical stimulation of the trachea in the cat. The effects of tachykinin NK1 receptor antagonists are still debated, whereas an inhibitory effect of SR 142801, a tachykinin NK3 receptor antagonist, has been reported against citric acid-induced cough in the guinea-pig. Experiments with tachykinin receptor antagonists which do not cross the blood brain barrier suggest that the site of action of tachykinin receptor antagonists is most probably peripheral, but a central action, at least in an area not protected by the blood brain barrier, cannot be excluded. Finally, tachykinin NK2 receptor stimulation seems to be involved in sensitisation of cough reflex.

Animals↗
PubMedDate not supplied

A tachykinin NK3 receptor antagonist, SR 142801 (osanetant), prevents substance P-induced bronchial hyperreactivity in guinea-pigs.

Aerosolized substance P (0.1 M, for 30 min) induced airway hyperresponsiveness in guinea-pigs 24 h after they were pre-treated with salbutamol (8.7 mM by aerosol for 10 min) and phosphoramidon (0.1 mM by aerosol for 10 min). This was displayed by an exaggerated response to the bronchoconstrictor effect of acetylcholine. A microvascular leakage hypersensitivity also occurred and was demonstrated by a potentiation of the plasma protein extravasation from bronchial vessels induced by histamine. The aim of this study was to investigate the effects of the non-peptide and potent tachykinin NK3 receptor antagonist, SR 142801 (osanetant), in comparison with those of the tachykinin NK1 and NK2 receptor antagonists, SR 140333 (nolpitantium) and SR 48968 (saredutant) respectively, on substance P. When given once at 1 mg/kg i.p. 45 min before exposure to substance P, SR 142801 prevented both hyperresponsiveness to acetylcholine and the potentiation of histamine-induced increase in microvascular permeability. SR 142801 did not exhibit any tachykinin NK1 or NK2 antagonistic activity in experiments on guinea-pig isolated airways, in vitro or in vivo. The results suggest that tachykinin NK3 receptors might be involved in these substance P-induced effects on airways.

Acetylcholine↗
PubMedDate not supplied

Adrenaline hypothesis: effect of formoterol on noradrenaline release.

1 Originally, the so-called 'adrenaline hypothesis' related the release of noradrenaline (NA) to stimulation of presynaptic beta2-receptors in nerve endings; now it confers a possible role to adrenaline taken up then released by nerves endings. It represents a potentially useful therapeutic pathway. The present study aims to investigate the effects of formoterol, a highly selective beta2-adrenoceptor agonist. 2 It was carried out in freely moving rats, the isotope dilution technique being used to measure the NA spill over rate (NA-SOR) and metabolic clearance rate (MCR). 3 A series of three results are reported. (a) When compared with adrenaline on equimolar basis, formoterol (2.3 micro kg-1 min-1) increased NA-SOR while mean arterial blood pressure was decreased and heart rate increased. Thus, it was difficult to separate a direct presynaptic effect from indirect baroreflex-dependent activation of the sympathetic system. (b) When formoterol was infused at 1 ng kg-1 min-1, a dose empirically defined to induce no haemodynamic effect, NA-SOR was significantly increased, while NA-MCR remained unchanged. (c) The NA-SOR response to formoterol was not amplified by the presynaptic alpha2-adrenoceptor blocker, yohimbine, in contrast to the NA-SOR response to adrenaline. 4 In conclusion, formoterol, a beta2-adrenoceptor agonist, is shown to increase the release and plasma concentration of NA while its clearance was not changed.

Adrenergic beta-Agonists↗
PubMedDate not supplied

[Approach to bronchial hyperreactivity in vitro].

The isolated human bronchus model is interesting for the study of drug-receptor interactions in 'normal' preparations. Several attempts have been made to prepare in vitro models of airway hyperresponsiveness close to the pathophysiology of asthma. In this paper, we shall present some results obtained with LPS and interleukin 1 beta (IL-1 beta). LPS (100 ng/ml, for 3 to 6 h) or IL-1 beta potentiated bradykinin and the tachykinin NK-1 selective receptor agonist [Sar9, Met-O2] SP -induced human isolated bronchi contraction in vitro (IL-1 beta 3 10(-10) M, at 37 degrees C for 1 to 3 h for bradykinin or at 21 degrees C for 15 h for [Sar9, Met-O2] SP in Krebs-Henseleit solution). As in control bronchi, the effects of bradykinin and of [Sar9, Met-O2] SP after interleukin 1 beta pre-treatment were abolished by indomethacin (10(-6) M), the thromboxane A2 receptor antagonist GR 32191 suggesting that prostanoids remain involved under these experimental conditions. Although bradykinin and [Sar9, Met-O2] SP -induced contractions were mediated by thromboxane receptor stimulation, the thromboxane A2 (TxA2) mimetic U46619 induced contraction of human bronchi was not enhanced by IL-1 beta pre-treatment. The cyclooxygenase 2 (cox 2) inhibitor GGP 28238 (10(-6) M) inhibited IL-1 beta-induced potentiation of [Sar9, Met-O2] SP but not of bradykinin effect. Bradykinin and [Sar9, Met-O2] SP induced a release of TxB2, the stable metabolite of TxA2, in the organ bath and this release was increased by IL-1 beta pre-treatment. Bradykinin-induced release of 6 keto prostaglandin F1 alpha (the stable metabolite of prostaglandin I2) was not enhanced by IL-1 beta. Taken together, our results suggest that IL-1 beta is able to potentiate the effect of bradykinin or tachykinin receptor agonists on the human isolated bronchus. Several mechanisms might be involved, including an increase of thromboxane synthase synthesis and/or activity in the case of bradykinin and of short term incubation (3 h, 37 degrees C) or an increase of synthesis and/or activity of cox-2 for tachykinin and for long-term incubation (15 h, 21 degrees C).

Asthma↗