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Biomedical subjects

P Demenge

Publications and source records attributed to P Demenge.

At least 37 records · Page 2Linked to original sources
PubMed1998

Myocardial beta-adrenergic reactivity in pressure overload-induced cardiac hypertrophy in the rat.

The purpose of this study was to evaluate the changes in myocardial beta-adrenergic reactivity in animals undergoing a 4 week cardiac pressure-overload. Abdominal aortic constriction (AAC) or sham operation (sham) were performed in male Wistar rats, and 4 weeks later, isoprenaline dose-effects (chronotropic, inotropic and lusitropic properties) were studied after pithing. Noradrenaline (NA) and adrenaline (A) concentrations and NA turn-over index (DHPG /NE ratio) were evaluated in heart ventricles, while beta-adrenoceptor characteristics in ventricle homogenates and slices with [125I]iodocyanopindolol and the beta (1)/beta (2)-adrenoceptor ratio were estimated. Four weeks of cardiac pressure overload resulted in a 70% increase in ventricle weight/body weight ratio (from 2.5 +/- 0.1 to 4.2 +/- 0.3 mg/g in sham and AAC rats, respectively) and a 24% increase in protein contents (from 11.3 +/- 0.7 to 14.0 +/- 1.1 mg/100 mg ventricle in sham and AAC rats respectively). The ventricle NA content was similar in AAC and sham, while the ventricle A content and NA turn-over index were significantly increased in AAC rats (35 and 80% vs sham, respectively). Dose response of isoprenaline was significantly shifted to the right for all studied effects in AAC rats. However, maximal response (in relative values) was similar in AAC and sham rats only for heart rate but not for parameters depending on left ventricle contractile response. The beta-adrenoceptor density was significantly decreased in AAC by 30% without apparent affinity change and due to decreases in beta (1)-sites in septum and to beta (1)- and beta (2)-adrenoceptors in left ventricle endocardium. Decreases in isoprenaline-induced cardiac responses in AAC rats are associated with beta (1)-adrenoceptor density reduction and modification of beta (1)- and beta (2)-adrenoceptor ratio. These modifications are not the only reason for such dose response changes, at least for contractile response.

Adrenergic beta-Agonists↗
PubMed1997

In vitro antiarrhythmic effect of prior whole body hyperthermia: implication of catalase.

The protective effect of heat stress against mechanical dysfunction and myocardial necrosis after prolonged ischemia is well known. We have investigated whether the protective effect of heat stress extends to reperfusion arrhythmias in the isolated perfused rat heart. Rats were exposed to 20 min of 42 degrees C hyperthermia. Twenty-four h later their hearts were isolated, perfused and subjected to a 5-min period of occlusion of the left coronary artery. The incidence and duration of reperfusion arrhythmias were assessed in the 30-min reperfusion period. Prior heat stress led to a reduction in the incidence (from 100 to 60%, P</=0.05) and duration (from 611+/-251 to 62+/-51 s, P</=0.05) of ventricular tachycardia and/or fibrillation, upon reperfusion following a 5-min ischemic period. This prevention of reperfusion arrhythmias was associated with a two-fold increase in endogenous catalase activity and an enhanced heat stress protein hsp 72 and 27 expression. Catalase inhibition by 3-amino triazole (AT) abolished the antiarrhythmic effect of heat stress. The incidence (80 v 100%) and duration (691+/-238 v 989+/-242 s) of reperfusion arrhythmias were not different between the group heat shocked + AT and the group treated only with AT. On the other hand, in the presence of AT, myocardial noradrenaline release was attenuated by prior heat stress (upon stabilization: 3.9+/-0.8 compared to 9.4+/-2.1 pg/ml/g tissue, P</=0.05; upon reperfusion: 42.7+/-7.3 compared to 69.8+/-9.5 pg/ml/g tissue, P</=0.05). In conclusion, heat stress leads to protection against reperfusion arrhythmias occurring after a short ischemic insult, in the isolated rat heart. Heat stress proteins and catalase seem to be implicated in this protective effect. Finally, we have shown that in presence of AT, heat stress decreases myocardial noradrenaline release.

Animals↗
PubMed1997

Reflex adrenal medullary secretion during coronary occlusion mediated by cardiac receptors with afferent vagal fibres in the rat.

The relative contribution of ventricular receptors and sinoaortic baroreceptors to the reflex release of adrenaline upon coronary occlusion was studied in anaesthetised rats submitted to a 30-min occlusion of the left coronary artery. Arterial adrenaline concentrations, heart rate and blood pressure were evaluated in control and sham-operated rats, and following sinoaortic denervation (SAD), bilateral vagotomy with and without SAD, ventricular application of lidocaine, neonatal treatment with capsaicin and cervical section of teh spinal cord. In all groups submitted to coronary ligation, blood pressure decreased sharply upon ligation and remained significantly reduced throughout occlusion while heart rate changes were not significant. In control rats, arterial adrenaline concentrations were significantly increased 15 and 30 minutes following coronary occlusion. The increase in adrenaline concentrations observed upon coronary ligation following SAD was not different from that of the control group. On the other hand, vagotomy with or without SAD, ventricular application of lidocaine, neonatal capsaicin treatment and spinal section all greatly reduced the increase in plasma adrenaline values. These results suggest that a large part of the reflex release of adrenaline upon coronary occlusion is mediated by ventricular receptors with unmyelinated vagal afferent fibres.

Adrenal Medulla↗
PubMed1994

Heterogeneous distribution of a fatty acid analogue uptake in the myocardium of aged rats.

The aim of this study was to determine the extent and location of damaged myocardial areas in senescent rats. The viability of myocardial cells was evaluated in virgin young (4 months old) and aged (29 months old) female Wistar rats by analysing the uptake of a slowly metabolisable radiolabelled fatty acid analogue, 15-p-iodophenyl-beta-methylpentadecanoic acid (IMPPA). The biodistribution of IMPPA was measured in various organs, and regional myocardial uptake was specifically assessed using quantitative autoradiography. Myocardial enzymatic activity and DNA content were also evaluated with nitro blue tetrazolium (NBT) and propidium iodide (PI) staining, respectively. In senescent rats, cardiac and renal IMPPA uptake showed a significant (50%) reduction compared with young adult rats and the uptake was not significantly changed in the liver, spleen, lungs, and skeletal muscle. Total ventricular NBT staining and IMPPA uptake were almost homogeneous in young adult rats, whereas they were very heterogeneous in aged rats. In the latter, approximately 11% of the total ventricular volume showed a significantly decreased (by 60% or more) IMPPA uptake compared with normal values, and this reduction was greater in ventricle base than in apex. The myocardial areas unlabelled or poorly labelled by IMPPA represented 4, 5, 6, and 21% of the right ventricular, left ventricular epicardial, septal, and left ventricular endocardial volume, respectively, and were poorly stained with NBT. In some of these areas, PI staining indicated the presence of living cells unable to pick up NBT staining. In conclusion, in young adult rats, no myocardial lesions were observed using three different labelling techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1993

Central dopaminergic origin of bromocriptine induced tachycardia in normotensive rats.

OBJECTIVES: This study was undertaken to investigate the mechanism of the tachycardic effect of bromocriptine, a specific dopamine D-2 receptor agonist, which is not abolished, as previously reported, by intravenous domperidone, a selective dopamine D-2 antagonist unable to cross the blood brain barrier. Two hypotheses were tested: (1) that the increase in heart rate after intravenous treatment with bromocriptine could be related to central dopamine receptor stimulation and (2) that it could be induced by a release of adrenaline from the adrenal medulla. METHODS: Changes in mean aortic pressure and heart rate, induced by treatment with 150 micrograms.kg-1 bromocriptine intravenously, were measured in conscious or anaesthetised normal or adrenalectomised rats submitted to various pretreatments. RESULTS: In conscious intact rats, intravenous bromocriptine decreased mean aortic pressure (-11 (SEM1) mm Hg) and increased heart rate (62(12)) beats.min-1). Both effects were prevented by intravenous pretreatment (0.3 mg.kg-1) with dopamine D-2 receptor antagonists able to cross the blood brain barrier, such as haloperidol, sulpiride, and metoclopramide. In anaesthetised rats, domperidone (50 and 20 micrograms.kg-1) given via a lateral cerebral ventricle abolished the bromocriptine induced tachycardia without affecting the hypotensive response. Both effects were unchanged after bilateral adrenalectomy but were completely abolished by intravenous haloperidol pretreatment (0.3 mg.kg-1) in conscious adrenalectomised rats. CONCLUSIONS: These results suggest that in anaesthetised and conscious normotensive rats, the bromocriptine induced tachycardia is not related to a release of adrenaline from the adrenal medulla but could be elicited by central dopamine D-2 receptor stimulation through a possible increase in cardiac sympathetic tone.

Adrenalectomy↗
PubMed1993

Cardiovascular responses to intrathecal dopamine receptor agonists after spinal transection in conscious rats.

OBJECTIVE: The cardiovascular responses to transient intrathecal administration of dopamine agonists were studied daily in chronically prepared rats that had been spinally transected or were sham operated. The goals were (1) to determine the group differences in evoked heart rate and arterial pressure responses and (2) to determine, within the transected group, whether or not the long term responses could be dissociated. The hypothesis tested is that cord transection releases a tonic inhibition of cardiovascular responsiveness independently of the mechanism of receptor hypersensitivity. METHODS: Changes in mean aortic blood pressure and heart rate induced by intrathecal administration of the mixed D1/D2 dopamine receptor agonist apomorphine (150 nmol per rat) were measured in conscious rats during a 10 d experimental period following spinal transection. RESULTS: Complete spinal transection did not affect aortic pressure but increased basal heart rate values by about 33% with respect to normal rats (p < 0.001). When apomorphine was injected caudally to the section (at T9-T10) but not rostrally (at T2-T4), it induced a 50% greater and an 800% more long lasting decrease in mean aortic pressure and a 230% greater and 70% more long lasting decrease in heart rate in spinal than in sham operated rats. These increases in cardiovascular responses were corroborated by a leftward shift of the apomorphine dose-response curves. They were also found after intrathecal administration of highly selective D1 and D2 receptor agonists fenoldopam (50 nmol per rat) and quinpirole (150 nmol per rat), and were specifically blocked by intrathecal haloperidol (27 nmol per rat), a non-selective dopamine antagonist. CONCLUSIONS: Complete spinal transection induces different increases in hypotensive and bradycardic responses to the stimulation of caudally located spinal dopamine receptors which could be due to the destruction of a tonically inhibiting spinal system rather than to hypersensitivity of the dopamine receptors.

Animals↗
PubMed1992

Increase in the hypotensive effect of bromocriptine induced by spinal transection in rats: contribution of spinal dopamine receptors.

Intravenous (i.v.) administration of bromocriptine (150 micrograms/kg) in conscious normotensive rats with chronic spinal cord transection (at T5-T7), pretreated or not with i.v. propranolol (0.5 mg/kg), induced significant decreases in mean arterial blood pressure (MAP) which were greater and longer lasting than those in intact rats (-15 to -20 as compared with -10 mm Hg) for 8 days after transection. To assess the spinal and/or peripheral origin of this phenomenon, rats were also pretreated with either i.v. (0.3 mg/kg) or intrathecal (i.t.; 93 nmol/rat; at T9-T10) administration of domperidone, a selective dopamine (DA)2 receptor antagonist incapable of crossing the blood-brain barrier (BBB) freely. The increase in hypotension induced by spinal section was suppressed by i.t. but not by i.v. domperidone. In intact rats, bromocriptine elicited an increase in heart rate (HR; approximately 50 beats/min more), which was prevented by i.v. propranolol treatment. In spinal cord-transected rats, however, it had a significant bradycardic effect (approximately 50 beats/min less), which was antagonized by i.t.-administered domperidone. These results suggest that enhancement of the hypotensive effects induced by systemic administration of bromocriptine after a complete thoracic spinal transection is fully mediated by spinal DA2 receptors. This finding may help explain the increased orthostatic hypotension induced by DA receptor agonists in Parkinsonian patients with spinal lesions.

Analysis of Variance↗
PubMed1991

Evaluation of cellular viability by quantitative autoradiographic study of myocardial uptake of a fatty acid analogue in isoproterenol-induced focal rat heart necrosis.

Previous studies led us to hypothesize that a fatty acid analogue, 15-p-iodophenyl-beta-methyl pentadecanoic acid (IMPPA or BMIPP), which is taken up but not quickly metabolized by heart cells, would be a more suitable tracer of cellular viability than thallium-201. Biodistribution studies of 1-14C-IMPPA in conscious, freely moving rats showed that the concentration ratio of radioactivity in the heart with respect to the blood was about 8 for at least 60 min after intravenous administration, permitting its use as a putative tracer in these conscious, freely moving rats. Thereafter, the myocardial uptake of 14C-IMPPA was studied in isoproterenol-treated rats (daily treatment for 10 days in order to induce cardiac hypertrophy and necrotic foci) with respect to control ones. Comparison of myocardial localizations by quantitative autoradiography of the uptake of 201Tl and 14C-IMPPA with that of triphenyltetrazolium chloride (TTC) staining enabled comparative evaluation of nutritional blood flow, localization and uptake of 14C-IMPPA and necrotic foci size. Distributions of 14C-IMPPA and 201Tl in control rats' hearts were homogeneous, like TTC staining. In infarcted hearts, areas of decreased 14C-IMPPA uptake were nearly the same (100% +/- 5%) as those unstained by TTC. These areas were larger than those showing a decrease in thallium uptake (about 70% +/- 5% of the total scar size). Therefore, IMPPA seems to be a more accurate and sensitive indicator of necrosis localization compared with thallium. It may be a useful agent for assessment of myocardial viability by single photon emission tomography (SPET) imaging.

Animals↗
PubMed1991

Contribution of spinal dopamine receptors to the hypotensive action of bromocriptine in rats.

Bromocriptine, a dopamine (DA) receptor agonist, has been reported to have hypotensive effects in anesthetized and conscious normotensive rats but its mechanism of action is still not fully understood. Therefore, we studied the changes in mean arterial blood pressure (MAP) and heart rate (HR) elicited by an intravenous (i.v.) administration of bromocriptine (150 micrograms/kg), in either pentobarbital-anesthetized or conscious normotensive rats, pretreated with either i.v. (0.3 mg/kg) or intrathecal (i.t.) (93 nmol) domperidone, a DA receptor antagonist that does not cross the blood-brain barrier. In these preparations, i.v. administration of bromocriptine elicited dose-dependent decreases in MAP and rises in HR. The hypotensive effect was antagonized partially by i.t. and fully by i.v. domperidone. However, the latter compound did not modify the tachycardia, which could be blocked by propranolol (0.5 mg/kg i.v.). In rats pretreated with the latter beta-adrenoceptor antagonist, bromocriptine produced only a decrease in blood pressure that was inhibited by i.v. and i.t. domperidone. These results suggest that, in anesthetized and conscious normotensive rats, the hypotension induced by systemic administration of bromocriptine is fully mediated by DA2 dopamine receptors, which are located partly within the spinal cord and partly in the peripheral circulation.

Anesthesia↗
PubMed1991

Hypotensive and bradycardic effects elicited by spinal dopamine receptor stimulation: effects of D1 and D2 receptor agonists and antagonists.

In anesthetized rats, intrathecal (i.t.) administration, at the upper thoracic level of the spinal cord of fenoldopam (a selective dopamine D1-receptor agonist) or quinpirole (a selective D2-receptor agonist) decreased blood pressure (BP) and heart rate (HR) in a dose-dependent manner. Apomorphine, a nonselective DA receptor agonist, produced similar effects. Apomorphine-induced hypotension was competitively antagonized by either SCH 23390 or remoxipride, selective D1- and D2-receptor antagonists, respectively, but only remoxipride antagonized the bradycardia. Furthermore, SCH 23390 antagonized the hypotensive effect of fenoldopam but did not change that induced by quinpirole. Remoxipride antagonized the hypotensive effect of quinpirole but did not alter the hypotensive effect of fenoldopam. Quinpirole-induced bradycardia was antagonized only by remoxipride. Bradycardia elicited by fenoldopam did not appear to be generated by dopamine receptor stimulation, as suggested by the lack of blocking effects of SCH 23390 and remoxipride. Data obtained with fenoldopam were corroborated with use of SK&F 38393, another dopamine D1-receptor agonist. We conclude that hypotensive effects of i.t.-administered DA receptor agonists appear to result from activation of spinal D1- and D2-receptors whereas bradycardia is related only to activation of spinal D2-receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Rostrocaudal localization of cardiovascular responses induced by intrathecal administration of apomorphine in conscious, freely moving rats.

In conscious freely moving rats, administration of apomorphine (179 nmol), a dopamine receptor agonist, into the intrathecal (i.t.) space decreased mean aortic blood pressure (MBP) and heart rate (HR). Both the magnitude and the time of appearance of the response varied according to the spinal level of administration. The largest and immediately appearing effect was observed after the injection at the upper thoracic site, whereas the magnitude of the responses was smaller with an immediate or slightly delayed (0.5-1.5 min) onset at lower thoracic and midcervical levels. More caudal responses appeared to be due to spreading of the drug along the spinal axis (onset in 1-2 min after administration). Behavioral responses (stereotyped movements) were observed within 2-3 min after administration and were nearly the same whatever the site of administration. These results corroborate, as do those provided by i.t. injections of tritiated apomorphine, the spinal origin of cardiovascular effects of i.t. apomorphine. Furthermore, spinal transection at the T5-T7 level did not change the magnitude and duration of decreases in MBP and HR elicited by i.t. apomorphine injected at the T2-T4 level. Moreover, this procedure enhanced responses to i.t. administration at the T9-T10 level. In conclusion, these results favor the existence of a spinal site of action for the cardiovascular effects of apomorphine. Furthermore, they indicate that spinal transection is accompanied by development of a hypersensitive phenomenon (of a mechanism to be determined).

Analgesics↗
PubMed1987

Cortical ablation fails to influence striatal dopamine target cell supersensitivity induced by nigrostriatal denervation in the rat.

The possible influence of the corticostriatal (glutamatergic) pathway on denervation-induced striatal dopamine target cell supersensitivity has been investigated in the rat by measuring the changes in striatal acetylcholine levels induced by the dopamine agonist pergolide and the basal dopamine D2-receptor density after combined 6-hydroxydopamine-induced lesion of the substantia nigra and cortical ablation. Lesion of the nigrostriatal dopaminergic pathway alone enhanced the ability of pergolide (0.06-1 mg/kg i.p.) to increase acetylcholine levels and increased the maximal density of [3H]spiperone binding sites in the striatum. Similar changes in these biochemical parameters were observed after combined cortical ablation and nigral lesion. Cortical ablation by itself slightly diminished acetylcholine levels and reduced by 30% [3H]spiperone binding site density in the striatum. These results indicate that the corticostriatal tract does not influence striatal dopamine target cell supersensitivity caused by dopaminergic denervation.

Acetylcholine↗
PubMed1985

Changes of the striatal 3H-spiperone binding 3-6 weeks after nigrostriatal denervation and after two years.

A complete unilateral lesion of the nigrostriatal pathway by 6-hydroxydopamine injection in the substantia nigra induced a drastic increase in striatal dopaminergic binding sites labelled by 3H-spiperone, 30 days after the lesion. This increase (75% over controls) was time restricted: it was only 39% and 34% over control values at respectively 25 and 35 days after the lesion. Furthermore, 45 days after the destruction of the substantia nigra, the density of labelled sites returned close to the homolateral control values, but remained higher than the contralateral ones, according to the right-left difference found in control animals. Quite later (2 years after the lesion), there was a decrease in the density of labelled sites as compared to the respective homolateral control levels. However, such binding sites tend to remain higher in the striatum of the lesioned side than in the striatum of the intact one, although such a difference was not statistically significant, being very close to the right-left asymmetry observed in control animals. Contrary to our previous results with 3H-Haloperidol, the apparent dissociation constant did not vary significantly, whatever the considered delay after the lesion. These results are discussed in the light of previous results obtained by others and by us.

Animals↗
PubMed1984

Cardiovascular effects in the rat of intrathecal injections of apomorphine at the thoracic spinal cord level.

Intrathecal (i.t.) administration of apomorphine at the upper thoracic level lowered blood pressure and heart rate in awake rats. This decrease was dose-dependent and competitively antagonized by haloperidol (i.v. and i.t.) or domperidone (i.t.) but not by domperidone (i.v.). Furthermore, these effects of apomorphine were not affected by alpha- and beta-blocking drugs (i.t.). The results suggest a spinal site, at least in part, for the cardiovascular effect of apomorphine.

Animals↗
PubMed1984

Time course of the changes in striatal acetylcholine levels induced by pergolide and haloperidol after lesion of the nigrostriatal dopaminergic pathways in the rat.

Lesion of the nigrostriatal dopaminergic pathway in the rat by 6-hydroxydopamine enhances the ability of pergolide to increase striatal acetylcholine levels and prevents the haloperidol-induced decrease in acetylcholine concentrations. This supersensitive response of striatal cholinergic cells is already maximal 6 days after lesion but tends to decrease thereafter. As the time course of the development of the supersensitivity of cholinergic cells differs from that of increased dopamine binding site density, the two are probably not causally related, the former reflecting rather a change occurring beyond the dopamine recognition site.

Acetylcholine↗
PubMed1981

Supersensitivity time course of dopamine antagonist binding after nigrostriatal denervation: evidence for early and drastic changes in the rat corpus striatum.

The sensitivity of the [3H]haloperidol binding technique can be greatly increased by focusing tissue sampling on striatal regions where dopaminergic innervation is the richest. Such sampling is provided from pooled microdiscs punched out of 8 serial 500 micrometer thick sections of the rat brain. With these conditions, the density of receptor sites (Bmax) was found to be twice that of the whole striatum, without modification of the apparent dissociation constant (Kd) and of the Hill's slope. Such a procedure applied to rats with complete 6-hydroxydopamine-induced unilateral nigrostriatal lesions showed a moderate decrease in Bmax in the lesioned side up to 6 days after surgery, whereafter the value of Bmax increased progressively up to the thirtieth day, being then 160% over the control value. Conversely, the apparent Kd decreased significantly from the second to the sixth day postsurgery in the lesioned side, and then increased moderately up to the tenth day and drastically from the twenty-first to the thirtieth day. No change was observed in the corresponding intact side. The modifications appeared chronologically compatible with those corresponding to the behavioral denervation supersensitivity, evidencing drastic binding changes as compared with the whole striatum. The unexpected variations in Kd observed were well correlated with those in Bmax, suggesting that the new available binding sites might be of lower affinity. In the light of all these results, a hypothetical model is proposed.

Animals↗
PubMed1981

Identification and distribution of neuroleptic binding sites in the rat spinal cord.

Identification of neuroleptic receptor sites in the rat spinal cord could be achieved by the binding of [3H]haloperidol to membranes taken from the different horns. The use of pooled frozen microdiscs punched from these different spinal cord areas allowed the detection of saturable stereospecific binding, as defined in the presence of (+)- and (-)-butaclamol. Comparison of the binding constants with those obtained in the corpus striatum resulted in similar dissociation constants and Hill's slopes. Maximal binding capacity was quite different, being the greatest in the whole striatum (157 +/- 8 fmol/mg protein) followed by the dorsal horn (56 +/- 3 fmol/mg protein) and the lateral (34 +/- 5 fmol/mg protein) and ventral ones (31 +/- 2 fmol/mg protein). The displacement of the labelled ligand by different dopaminergic and nondopaminergic drugs at various concentrations gave similar results in the whole striatum and the spinal cord, giving further support for the existence of a dopaminergic innervation of the spinal cord and showing that dopaminergic receptor sites are distributed through the different spinal horns, with a maximal density in the dorsal horn--as for dopamine levels. No detectable stereospecific binding could be obtained from the surrounding spinal white matter, even at high tissue concentrations. Owing to poor sensitivity of the binding technique, no stereospecific neuroleptic binding could be demonstrated in the whole spinal cord, even at very high tissue concentration, whereas it could be detected in spinal cord tissue sampled from restricted areas of dense dopaminergic innervation.

Animals↗