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Jean-Michel Senard

Publications and source records attributed to Jean-Michel Senard.

24 records · Page 2Linked to original sources
PubMed2003

Adrenomedullin upregulates M2-muscarinic receptors in cardiomyocytes from P19 cell line.

1. The effects of AM on expression of muscarinic (M) receptors from P19-derived cardiomyocytes were examined. 2. RT-PCR experiments revealed expression of M(1)-M(4) receptor genes. Immuno-histochemistry indicated that M(2) expression is restricted to contractile cells. Carbachol inhibition of isoprenaline-induced increase in beating rate was prevented by atropine and methoctramine (pA(2): 8.1). Inhibition of [(3)H]-NMS binding by atropine (pK(i): -8.4+/-0.2) and methoctramine (pK(i): -8.3+/-0.2) suggests that M(2) is the functional expressed isoform. 3. [(3)H]-NMS binding and semiquantitative RT-PCR studies showed a dome shaped time course of M(2) expression with a maximum at 7 days of differentiation followed by a progressive decline. 4. AM concentration-dependently upregulated M(2) receptor mRNA during late differentiation stages in P19 cells but also in rat atrial cardiomyocytes. This effect was potentiated by factor H. AM (100 nM) plus factor H (50 nM) treatment of P19 cells for 24 h significantly increased [(3)H]-NMS-specific binding (B(max): 81+/-7 vs 31+/-6 fmol mg(-1) prot). The effect of AM on mRNA levels was prevented by AM receptor antagonist AM(22-52) (1 micro M) but not by CGRP antagonist, CGRP(8-37) (1 micro M). 5. The mRNA levels encoding CRLR receptor declined with culture duration, whereas those encoding L1/G10D receptor remained stable. 6. Our findings demonstrate that AM regulates M(2) receptors expression in cardiomyocytes probably through a mechanism involving L1/G10D receptors. The 'in vivo' significance of this phenomenon remains to be demonstrated.

Adrenomedullin↗
PubMed2003

High isoproterenol doses are required to activate beta3-adrenoceptor-mediated functions in dogs.

The "in vivo" conditions for beta3-adrenoceptors (beta-AR) activation by isoproterenol were investigated in dog. Experiments were carried out in anesthetized dogs using isoproterenol as a nonselective beta-AR agonist. Intravenous infusion of isoproterenol (0.4 nmol/kg/min) induced arterial hypotension and tachycardia with a slight decrease in cutaneous blood flow. At this dose, isoproterenol increased glucose, glycerol, and nonesterified fatty acid plasma levels. The changes in cardiovascular and endocrine-metabolic parameters, induced by the low dose of isoproterenol, were suppressed by pretreatment with nadolol (1 mg/kg, i.v.). After nadolol administration, however, a 10-fold higher dose (4 nmol/kg/min) of isoproterenol was able to induce a decrease in arterial blood pressure with a slight tachycardia and an increase in cutaneous blood flow. This high dose of isoproterenol increased nonesterified fatty acid and glycerol plasma levels but failed to change glucose plasma levels. All these effects were abolished by a pretreatment with nadolol (1 mg/kg, i.v.) plus SR59230A [a selective beta3-adrenoceptor antagonist; (3-(2-ethylphenoxy)-1(1S)-1,2,3,4-tetrahydronaphth-1-ylaminol-(2S)2-propanol oxalate); 1 mg/kg, i.v.]. Moreover, as observed with the high dose of isoproterenol under nadolol pretreatment, an infusion of SR58611A [a selective beta3-adrenoceptor agonist; ((N2S)-7-carbethoxymethoxy-1,2,3,4-tetrahydronaphth-2-yl-(2R)-2-hydroxy-2-chlorophenyl) ethanamine hydrochloride] induces a decrease in mean arterial blood pressure associated with an increase in heart rate, cutaneous blood flow, and nonesterified fatty acid and glycerol plasma levels. These results demonstrate that the in vivo activation of beta3-adrenoceptors requires higher doses of catecholamine than those necessary for beta1- and/or beta2-adrenoceptor stimulation. These results also argue for the lack of a beta3-AR involvement in the control of heart rate and glycogenolysis in dogs.

Adrenergic beta-Agonists↗
PubMed2002

Alpha2 -adrenoceptor function in arterial hypertension associated with obesity in dogs fed a high-fat diet.

OBJECTIVE: To investigate the status of alpha2-adrenoceptors in a model of obesity-related arterial hypertension. DESIGN: A parallel study in dogs randomly assigned to a high-fat diet (HFD group, n = 6) or normal canine food (controls, n = 6) for 9 weeks. METHODS: Postsynaptic vascular alpha2-adrenoceptors were assessed through analysis of dose-pressor responses to clonidine [2.5, 5.0 and 15.0 microg/kg intravenously (i.v.)] after muscarinic, beta- and alpha1-adrenergic receptor blockade. Presynaptic and central alpha2-adrenoceptors were studied through measurement of changes in plasma concentrations of catecholamine induced by yohimbine (0.05 mg/kg i.v.). The number of platelet alpha2-adrenoceptors (expressed as fmol/mg protein) and the percentage in a state of high affinity were measured using [3H]RX821002. RESULTS: Clonidine, when administered to dogs that were under autonomic blockade, elicited a dose-dependent increase in blood pressure. The doses of clonidine required to induce a 50% maximum increase in systolic and diastolic blood pressures remained unchanged after 9 weeks of a high-fat diet (systolic: 6.0 +/- 0.3 microg/kg at baseline and 5.6 +/- 0.2 microg/kg after 9 weeks; diastolic: 4.2 +/- 0.2 microg/kg at baseline and 3.9 +/- 0.2 microg/kg after 9 weeks). After 9 weeks of the regimen, plasma concentrations of noradrenaline were significantly greater in the HFD group than in controls (337 +/- 22 pg/ml compared with 212 +/- 37 pg/ml). The increment in plasma concentrations of noradrenaline elicited by yohimbine after 9 weeks was smaller in the HFD group than in controls (93 +/- 44% compared with 181 +/- 46%; P = 0.024). In the HFD group, the number of platelet alpha2-adrenoceptors and the percentage that were in a state of high affinity were significantly lower after 9 weeks, compared with baseline (number: 239 +/- 21 fmol/mg protein at baseline and 95 +/- 7 fmol/mg protein after 9 weeks; high-affinity: 30 +/- 3% at baseline and 21 +/- 4% after 9 weeks; P < 0.05). CONCLUSIONS: These results suggest that presynaptic or central alpha2-adrenoceptor function, or both, is specifically impaired after 9 weeks of a high-fat diet. These modifications may account for the development of arterial hypertension in this model.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

[Drugs, Parkinson's disease and parkinsonian syndroms: recent advances in pharmacovigilance].

This paper reviews recent data on the pharmacovigilance of antiparkinsonian drugs and drugs inducing parkinsonian syndroms. Sudden sleep attacks were first described in 1999 with dopamine agonists. In fact, they can be induced by all the dopaminergic antiparkinsonian drugs. Favorising factors are duration of the disease, dose of dopaminergic drugs, daytime somnolence or dysautonomia. This adverse drug reaction can be serious leading, for example, to road accidents. Cardiac valvulopathies were more recently (end of 2002) described with pergolide. Thus, this dopamine agonist should now be prescribed as a last choice among dopamine agonists. Dopamine drugs (levodopa as well as dopamine agonists) can induce hypersexual behaviours or pathological gambling. Among the long list of drugs inducing parkinsonian syndroms, recent data suggest the involvement of serotoninergic antidepressants, valproic acid and trimetazidine. Finally, these data on pharmacovigilance allow to precise the physiological role of dopamine: beside its motor and psychic effects, dopamine is also involved in the sleep-arousal control. It is also an important mediator for pleasure, hedonic regulations and sexual behaviour. This review also underlines the major role of spontaneous reports to the pharmacovigilance systems to identify new adverse drug reactions.

Accidents, Traffic↗
PubMedDate not supplied

Prevalence and costs of parkinsonian syndromes associated with orthostatic hypotension.

OBJECTIVE: To measure the frequency of and direct costs related to parkinsonian syndromes associated with orthostatic hypotension (OH). PATIENTS/METHODS: Patients over 45 years using at least one antiparkinsonian drug (excluding piribedil or anticholinergics prescribed alone) were identified from the Haute-Garonne Social Security prescription database and separated in two groups according to simultaneous prescription (OH group) or not (control group) of drugs for orthostatic hypotension. Direct medical costs were analysed retrospectively, over a 6-month period, from the health care payer's perspective. RESULTS: Eighty-eight patients (9.1%) out of 971 parkinsonian also received antihypotensive drugs. Direct medical costs were significantly higher in OH than in control group (4.425 vs. 3.074 Euro/patient/6 months, p < 0.05). Beside hospitalisation and ancillary cares, drugs accounted for highest expenses (989 vs. 781 Euro/patient/6 months in control group) since use of controlled-release levodopa formulations or dopamine agonists was higher in OH group. CONCLUSION: Occurrence of OH is associated with higher medical expenditure in parkinsonian syndromes.

Antiparkinson Agents↗