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Biomedical subjects

N Oudart

Publications and source records attributed to N Oudart.

34 records · Page 2Linked to original sources
PubMed1992

Bronchodilator action of an agonist for histamine H3-receptors in guinea pig perfused bronchioles and lung parenchymal strips.

Isolated guinea pig perfused bronchioles and lung parenchymal strips were examined as an in vitro model for assessment of the direct effect of pharmacologic agents on the airway smooth muscle. The experiments were performed with a perfusion technique in bronchioles, the input pressure being measured as an index of the state of dilation, while changes in tension of the lung parenchymal strips were measured with an isometric force transducer. In both preparations, histamine and acetylcholine elicited dose-related contractile responses whereas fenoterol induced a concentration-dependent relaxation. After the 3 agonists' activities were compared in these 2 preparations, we tested the intrinsic effects of a specific H3 agonist, (R) alpha-methylhistamine ([R] alpha-MeHA). Statistical analysis was by Student's t test on the Emax (expressed as a percentage of 10(-4) M papaverine relaxation), EC50, and slopes of regression lines calculated from the concentration-response curves plotted for (R) alpha-MeHA alone or in presence of antagonists. Our results showed that (R) alpha-MeHA induced a concentration-dependent relaxation of perfused bronchioles and lung parenchymal strips competitively inhibited by 10(-7) M thioperamide (H3-antagonist), whereas 10(-5) M cimetidine (H2-antagonist) failed to prevent this effect. These results suggest the presence of H3-histaminergic dilatory receptors in the guinea pig airway.

Acetylcholine↗
PubMed1992

Endothelium-dependent relaxation of rabbit middle cerebral artery to a histamine H3-agonist is reduced by inhibitors of nitric oxide and prostacyclin synthesis.

1. The possible involvement of prostanoids and endothelium-derived relaxing factor (EDRF) in the vasodilatation induced by a histamine H3-agonist was examined in the rabbit perfused middle cerebral artery preconstricted with K+ (50 mM). 2. The endothelium-dependent relaxation to (R)-alpha-methylhistamine [(R)-alpha-MeHA] was competitively antagonized by thioperamide (an H3-antagonist) with a pA2 of 9.05, but unaffected by propranolol, atropine, L- and D-sulpiride. This effect was stereoselective since the (S)-isomer was 100 times less potent than the (R)-isomer. 3. Two inhibitors of nitric oxide synthesis, NG-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA), inhibited the relaxation induced by (R)-alpha-methylhistamine. The inhibitory effects of 10(-5) M NG-nitro-L-arginine methyl ester and 10(-5) M NG-monomethyl-L-arginine were reversed by equimolar concentrations of L-arginine, but strongly enhanced by 10(-4) M tranylcypromine. Tranylcypromine alone (10(-5) M-10(-4) M) partially reduced the (R)-alpha-methylhistamine-induced relaxation. Both dexamethasone and indomethacin also inhibited this relaxation. 4. The results suggest that the H3-mediated relaxation of the rabbit middle cerebral artery may involve release of both a prostanoid, probably prostacyclin, and endothelium-derived relaxing factor. The relaxant effects of these two endogenous compounds appear to be synergistic.

Animals↗
PubMed1990

Naftidrofuryl inhibits contractions to serotonin in intact and de-endothelialized cerebral arteries in vitro.

Excised segments of rabbit middle cerebral artery were cannulated and perfused in vitro at constant flow (1 ml/min). In vessels with intact endothelium, integrity of the intima was checked by determining relaxations to acetylcholine. In another series of segments, the endothelium was destroyed mechanically. Serotonin (5-HT) was added to the perfusate in increasing concentrations (3 x 10(-10) to 10(-4) M). Perfusion pressure served as the index of vasomotor responses of the arterial segment. At therapeutic concentrations, the 5-HT2 antagonist naftidrofuryl did not change perfusion pressure of normal vessels in the absence of 5-HT. Addition of 5-HT to intact vessels had no effect on perfusion pressure, but potentiated the contraction induced by KCl. This reaction was greatly amplified after de-endothelialization. Addition of naftidrofuryl (10(-7) M) to the perfusate strongly inhibited 5-HT's contracting effects on both intact and deendothelialized arterial segments. Naftidrofuryl at 10(-6) M further displaced the dose-effect curve to the right in a competitive manner. These data confirm the potentiating effect of 5-HT on vascular smooth muscle (even in intact vessels) and the anticonstricting effects of naftidrofuryl when 5-HT2 receptors on smooth muscle cells are activated by serotonin.

Animals↗
PubMed1988

A highly potent and selective H3 agonist relaxes rabbit middle cerebral artery, in vitro.

An H3-agonist, R alpha methylhistamine strongly relaxed isolated and perfused rabbit middle cerebral artery precontracted with K+. This vasodilatation was not antagonized by either mepyramine or cimetidine but was competitively antagonized by an H3-antagonist, a mixture of impromidine and cimetidine. Histamine activated the H3-sites in this artery since its concentration-response curve (obtained with mepyramine and cimetidine) was parallel to that of R alpha methylhistamine. Our data indicate that H3-sites could exist in the rabbit cerebral artery.

Animals↗
PubMed1988

Relaxation of rabbit middle cerebral arteries in vitro by H1 histaminergic agonists is inhibited by indomethacin and tranylcypromine.

The H1-histaminergic agonists 2-pyridylethylamine (2-PEA) and 2-methylhistamine relaxed potassium-constricted, perfused, rabbit middle cerebral arteries at low concentrations (3 x 10(-11) to 3 x 10(-8) M) and constricted them at high concentrations (3 x 10(-7) to 3 x 10(-4) M). The relaxation and the contraction were not antagonized by propranolol (up to 3 x 10(-6) M) given 30 min before, suggesting that beta-adrenergic mechanisms were not involved. When 2-PEA was tested on arteries constricted with uridine triphosphate (UTP), similar results were obtained. In the UTP-constricted arteries, the 2-PEA-induced responses were competitively antagonized by 3 x 10(-9) M mepyramine. Together with previous work (Ea Kim et al., 1986), these results are compatible with the hypothesis that H1-receptors were responsible for both the relaxation and the contraction observed. When either indomethacin (10(-8), 3 x 10(-7), or 10(-5) M), dexamethasone (10(-5) M), or tranylcypromine (10(-5) or 10(-4) M) were tested on the response to 2-PEA or 2-methylhistamine, these inhibitors suppressed the relaxation or reversed it to a contraction. Furthermore, they potentiated the contraction induced by these agonists. These results favour the hypothesis that the H1-mediated relaxation in rabbit cerebral arteries may in part involve the release of prostaglandins, especially prostacyclin. The participation of such a prostanoid in histaminergic relaxation seems exclusively an H1-mediated mechanism, since the relaxation induced by the H2-agonist dimaprit (in the presence of mepyramine) was not antagonized by either indomethacin (3 x 10(-7) M) or tranylcypromine (10(-4) M).

Animals↗
PubMed1986

Histamine-induced constriction and dilatation of rabbit middle cerebral arteries in vitro: role of the endothelium.

We studied the effects of histamine on perfused rabbit middle cerebral arteries in vitro. Intact and endothelium-denuded preparations were compared. Histamine caused concentration-dependent constrictions in intact vessels which were competitively inhibited by an H1 receptor antagonist. This constriction was potentiated by either H2-receptor blockade or endothelium denudation. The greatest potentiation was observed with intraluminal as opposed to extraluminal administration. The H1 receptor agonist pyridylethylamine induced similar concentration-dependent constriction in intact and denuded preparations. After preconstriction, histamine, in the presence of an H1 receptor antagonist, dilated intact vessels to a maximum of 45.1%, and endothelium-denuded vessels to a maximum of 22% (p less than 0.02). We conclude that rabbit middle cerebral arteries possess H1 constrictory and H2 dilatory receptors, and that many of the H2 dilatory receptors are situated on the endothelial cells.

Acetylcholine↗
PubMed1986

Participation of vascular H1-receptors in histaminergic relaxation of rabbit middle cerebral artery in vitro.

4-Methylhistamine relaxed potassium-constricted perfused rabbit middle cerebral arteries at low concentrations (3 X 10(-11) - 3 X 10(-8) M) and constricted them at high concentrations (3 X 10(-7) - 10(-4) M). The relaxation was antagonized by either cimetidine (3 X 10(-7) or 10(-6) M) or mepyramine (3 X 10(-8) M) given 20 min before testing a series of increasing concentrations of 4-methylhistamine, whereas the constriction was slightly potentiated by cimetidine and reversed by mepyramine. The reduction of relaxation was enhanced by a combination of both blockers. These results suggest the involvement of both H1- and H2-receptors in the 4-methylhistamine-induced relaxation. When dimaprit was compared with 4-methylhistamine, it acted only as a relaxing agent, not as a constricting agent. The dimaprit-induced relaxation was antagonized by either cimetidine (3 X 10(-7) M) or mepyramine (3 X 10(-8) M). The inhibition of relaxation was enhanced with a combination of both blockers. This supports the hypothesis that the dimaprit-induced relaxation in the rabbit cerebral artery is also mediated through both H1- and H2-receptors. The H1-agonists 2-methylhistamine and 2-pyridyl ethylamine induced two kinds of responses: an initial relaxation at low concentrations which was reversed by mepyramine (3 X 10(-8) or 10(-6) M) but not by cimetidine (10(-6) or 10(-5) M); this relaxation was followed at higher concentrations by a vasoconstriction which was antagonized by mepyramine (3 X 10(-8), 3 X 10(-7) or 10(-6) M) but not by cimetidine (10(-6) or 10(-5) M). Relaxation by these agents therefore seems to involve the participation of H1-receptors. The pharmacological effects of the histaminergic agonists and antagonists used could be explained by assuming that a distinction exists in the rabbit middle cerebral artery between the receptors concerned in H1-mediated relaxation and H1-mediated constriction.

Animals↗
PubMed1985

Pial artery responses to norepinephrine potentiated by endothelium removal.

The effect of endothelium removal on pial artery constriction in response to norepinephrine (NE) was studied in vitro using a perfused vessel setup in which pressure increases indicate vasoconstriction. In deenodothelialized rabbit arteries, the reaction to extraluminal NE was found to be characterized by a much higher Emax (2.0 times) and a slight (but significant) leftward shift of the concentration-response curve (lower EC50) compared with control vessels. In cat arteries subjected to either extra- or intraluminal NE, the Emax was also substantially higher in deendothelialized preparations (4.4 and 5.1 times, respectively), but there was no significant difference in the EC50 values. Anatomical verification and functional tests (acetylcholine-induced dilatation) confirmed the presence and the absence of the endothelium in control and lesioned arteries, respectively. This modulatory influence of the endothelium may be of importance in cerebrovascular pathology.

Animals↗
PubMed1983

Relaxation of rabbit cerebral arteries in vitro by clonidine. Evidence of H2-receptor mediation.

The action of the antihypertensive agent, clonidine, was studied in a perfused preparation of rabbit middle cerebral arteries (MCA) in vitro. The MCA segments (8 mm long) were perfused at constant flow, the perfusion pressure upstream being monitored as an index of smooth muscle tone. In both normal (K+ = 2.7 mM) and high potassium (K+ = 30 mM) solutions, clonidine (3.10(-10) - 10(-4) mol.l-1) relaxed the arteries in a concentration-dependent manner. Expressed as a percentage of the maximum relaxation obtained in normal and high K+ solution with 10(-4) mol.l-1 papaverine, the Em was 79 +/- 3.9% (mean +/- SEM) and 63.7 +/- 2.4% respectively, and the EC 50 (4.3 +/- 2.0) 10(-8) mol.l-1 and (1.3 +/- 1.0) 10(-8) mol.l-1 respectively. The action of 6 specific antagonists at 3.10(-6) mol.l-1 was tested on the relaxation obtained in high potassium solution. The concentration-response curve was shifted to the right in a parallel manner, compatible with competitive inhibition, only by the H2-antagonist, cimetidine. Phentolamine and especially propranolol depressed the Em, suggesting antagonism by non-specific mechanisms. Methysergide and sulpiride induced no significant change in Em, but slightly displaced the curve in a nonparallel manner. Yohimbine had no effect on the relaxation. These results are interpreted as indicating that clonidine relaxes rabbit cerebral arteries in vitro, even at low, therapeutic concentrations, possibly by acting on H2-histaminergic receptors.

Adrenergic alpha-Antagonists↗
PubMed1981

[Urinary N-acetyl-beta-glucosaminidase as index of renal toxicity (author's transl)].

Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) has been studied in rats submitted to potentially nephrotoxic drugs (acetylsalicylic acid, gentamicin). Both drugs induced increase in NAG excretion which was reversible and dose-dependent. The date presented in this paper suggest that urinary NAG determination may have value as screening device for the study of nephrotoxic effects in experimental toxicology.

Acetylglucosaminidase↗
PubMed1981

Relaxation by dopaminergic agonists in cerebral and peripheral arteries (in vitro).

The receptors involved in dopamine-induced relaxation were investigated in whole segments of rabbit middle cerebral (M.C.A.) and central ear arteries (C.E.A.) by measuring pressure changes in a constant-flow in vitro set-up. Drug administrations were made in the perfusate. During treatment with high-K+ solution to induce active contraction, and in the presence of 3 x 10(-5) M phenoxybenzamine to prevent alpha-adrenergic contractions, cumulative concentration-response curves were obtained for dopamine, apomorphine, bromocriptine and piribedil. The effects of the dopamine receptor antagonists, sulpiride, haloperidol and droperidol, and a beta-adrenergic antagonist, propranolol, were tested on the concentration-response curves obtained with dopamine. The results can be summarized as follows: the dopaminergic agonists had a relaxant effect in 50% of C.E.A. and in 70% of M.C.A. after alpha-adrenergic receptor blockade. This effect was blocked by the 3 antagonists in the M.C.A., and this antagonism appeared to be competitive in the case of sulpiride. In the C.E.A., haloperidol and droperidol exerted complex effects on the dopamine relaxation, and sulpiride had inconsistent effects. Propranolol reduced the concentration-dependent relaxation in the C.E.A., but did not modify the relaxant effect of dopamine in the M.C.A. The present results are consistent with the hypothesis that dopaminergic agonists relax cerebral arteries by acting on specific receptors. The relaxant action on the C.E.A. seems more complex and may occur partly via beta-adrenergic receptors.

Animals↗
PubMed1976

[Determination of lead in foodstuffs and tobacco].

A large variety of food containing lead, food is for us an important source of contamination. The average quantity of lead contained in food and tobacco has been established yet. Thanks to these results, we known the exact quantity absorbed by men in normal conditions of living. We are working to establish its dosage with atomic absorption spectrophotometry.

Food Analysis↗
PubMedDate not supplied

[Determination of lead by atomic absorption spectrophotometry with regard to toxicology research].

The toxicity of lead in the human environment is acquiring a growing interest which lead us to choose a quick, precise, sensitive and specific method able to perform number of measurements. Thanks to the survey consisting in a dosage of lead by atomic-absorption spectrometric, we are able to confirm the advantages and superiority of such a method and to employ it for the toxicologic research of lead in food, water, industrial atmosphere, and biological liquids.

Chemical Phenomena↗