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Biomedical subjects

B Renaud

Publications and source records attributed to B Renaud.

At least 109 records · Page 6Linked to original sources

Effects of chronic beta-blocker treatment on catecholamine levels in spontaneously hypertensive rats.

In the present work the effects of a 55-day oral treatment with two beta-blocking agents (propranolol 40 mg/kg per day and S 2395 20 mg/kg per day) on the catecholamine (CA) content of central and peripheral structures were studied in spontaneously hypertensive rats (SHR). The concentrations of dopamine (DA), noradrenaline (NA) and adrenaline (A) in different structures dissected out from treated and control SHR were measured by a radioenzymatic method. At the peripheral level, no change in the concentration of NA (in the heart) or A (in the adrenal medulla) was observed. Propranolol increased the DA concentration in the C1 and C2 regions of the medulla oblongata and S 2395 increased the DA concentration only in the C2 region. In these two areas, the NA and A levels were unchanged. Both propranolol and S 2395 increased the DA, NA and A content in the locus coeruleus and in the anterior hypothalamus. On the contrary, there was no modification in the posterior hypothalamus. The anatomical specificity of these alterations of the CA levels suggests that they could be related to a specific action of beta-blockers on central catecholaminergic structures in SHR which might be linked to the antihypertensive effects of these drugs.

Adrenergic beta-Antagonists↗

Increased tyrosine hydroxylase activity in central adrenaline neurons after reserpine treatment.

By using preferential microdissection of the adrenaline (A) and noradrenaline (NA) neurons within the A2-C2 region of the rat medulla oblongata, it was possible to study the biochemical response of these two neuronal populations to reserpine administration. Three days after reserpine injections (10 mg/kg s.c., per day for 3 days), tyrosine hydroxylase (TH) activity was increased in the adrenergic C2 region whilst no change was observed in the noradrenergic A2 region. The response of the A neurons to reserpine was of lesser magnitude than the increase in TH activity observed under the same conditions in the NA neurons of the locus coeruleus and of the A5 region, and was likely to have originated in the A cell bodies. In contrast with previous studies, this work suggests that the A-containing neurons are responsive to reserpine administration, despite the lack of change in phenylethanolamine-N-methyltransferase activity.

Animals↗

Time course study of changes in the activity of the catecholamine synthesizing enzymes in the rat medulla oblongata after intraventricular injection of 6-hydroxydopamine.

Recent data have shown that 5 days after intraventricular injection of 6-hydroxydopamine (6-OHDA), the tyrosine hydroxylase activity (TH) was increased within the locus coeruleus (LC). We sought to determine if such an alteration occurs within the A1 and A2 noradrenergic (NA) and C1 and C2 adrenergic (A) neurons of the rat medulla oblongata. The TH activity within the cell bodies was significantly increased 2 days after 6-OHDA injection with a maximum at 5 days (LC, + 109%, P less than 0.001; A1-C1, + 40%, P less than 0.01; A2-C2; + 24%, P less than 0.01) while a significant decrease was present 21 days after 6-OHDA. Conversely, dopamine-beta-hydroxylase (DBH) activity exhibited a decrease which was maximal at 21 days (LC,-41%; A1-C1,-33%; A2-C2,-35%, P less than 0.001). Both the TH (-47% at 5 days) and the DBH (-82% at 12 days) activities were decreased within the terminals of the tractus intermediolateralis (TIML). The phenylethanolamine-N-methyltransferase (PNMT) activity was never altered in the cell bodies nor in the terminals analyzed. These data demonstrate that the NA neurons of the rat medulla oblongata and of the LC exhibit a similar pattern of response to the neurotoxin 6-OHDA. Conversely, the lack of change in the PNMT activity confirms the hypothesis of a resistance of the A neurons to 6-OHDA or questions the validity of the PNMT as an A marker.

2-Hydroxyphenethylamine↗

Distribution of tyrosine hydroxylase, dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase activities in coronal sections of the rat lower brainstem.

The activities of the three major catecholamines synthesizing enzymes were determined on supernatants from microcubes dissected out from 500 microns thick coronal sections of the rat lower brainstem. The microcubes exhibiting significant or high enzymatic activities represented only one-third of the microcubes analyzed and were generally localized either in the dorso-medial or in the ventro-lateral region of the lower brainstem. In the ventro-lateral region, referred to as the A1-C1 region, the rostro-caudal distribution of the enzymatic activities exhibited a small difference between the maximal TH and DBH activities and the maximum PNMT activity located 500 microns more rostrally. Conversely, in the dorso-medial region, referred to as the A2-C2 region, there was a much larger rostro-caudal difference (about 1500 microns) between the peaks of TH and DBH activities and the more rostral peak of PNMT activity. Such a distribution suggests a separation between the adrenaline (A) and the noradrenaline (NA) containing neurons within the dorso-medial region. According to the results of this study, a preferential microdissection of the A versus NA neurons seems possible in the A2-C2 region of the rat medulla oblongata.

Animals↗

Increase in noradrenaline-synthesizing enzyme activity in medulla oblongata in Parkinson's disease.

Dopamine beta hydroxylase (DBH), The noradrenaline-synthesizing enzyme, and phenyl-ethanolamine-N-methyltransferase (PNMT), the adrenaline-synthesizing enzyme, were assayed in 18 areas of brain stem in eight cases of parkinsonian syndromes and of four age- and postmortem delay-matched controls. Dissection was performed by the "punch" technique and enzyme activities assayed by radiometric methods. No significant change was found for PNMT activity. DBH activity was significantly increased in the A2-C2 area of the medulla oblongata (including the nucleus tractus solitarius) in the cases of Parkinson's disease. The A2-C2 area is known to be implicated in the control of blood pressure in rats. These findings are discussed in relation to orthostatic hypotension and the influence of L-dopa therapy.

Aged↗

Comparative microdistribution of the activity of catecholamine-synthesizing enzymes in horizontal sections of the rat lower brainstem.

The activities of the three major catecholamine-synthesizing enzymes were determined in brain tissue pellets dissected from 500-micrometers thick horizontal sections of rat lower brainstem. The rostrocaudal distributions of the three enzymatic activities were generally not parallel, suggesting differences in the respective localization of the noradrenergic and adrenergic neurons. The difference was most important in the A2-C2 region where the maximal activity of phenylethanolamine-N-methyltransferase (EC 2.1.1.28) was located 1.5 mm more rostrally than the maximal activities of the tyrosine hydroxylase (EC 1.14.16.2) and dopamine beta-hydroxylase (EC1.14.17.1). This result indicates that a more specific dissection of the adrenergic and noradrenergic neurons could be performed in the A2-C2 area of the rat brainstem.

Animals↗

[Regression of the cerebellar syndrome under long-term administration of 5-HTP or the combination of 5-HTP and benserazide. 26 cases quantified and treated using computer methods].

A quantitative evaluation of cerebellar ataxia, with an ataxia score (total, static, kinetic) and the measurement of objective values related to the major symptoms, is proposed. 21 patients with heredo-ataxias were treated for 12 months with high doses (16 mg/kg/day) of D-L-5-HTP, L-5-HTP or the association D-L-5-HTP (16 mg/kg/day)-Benserazide(6 mg/kg/day). A computerized processing of the data obtained by regular examination was performed. The ataxia showed a significant regression at the 12th month, mainly in the static performances and in the speed of speech. L-5-HTP appeared to be more active than D-L-5-HTP. The regression of the cerebellar ataxia was also observed in non degenerative conditions such as multiple sclerosis and surgical injury of the anterior lobe vermis, showing that 5-HTP was active on the cerebellar syndrome in general. The regression of the cerebellar ataxia was very slow in inherited diseases and continued for 2 or 4 months after the treatment stopped. A serotoninergic cerebellar control of motricity is discussed.

5-Hydroxytryptophan↗

Cerebrospinal fluid adenosine 3',5'-monophosphate, 5-hydroxyindoleacetic acid and homovanillic acid in patients with sleep apnoea syndrome.

Adenosine 3',5'-monophosphate (cyclic AMP), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were determined in the cerebrospinal fluid of patients with respiratory disorder and hypersomnia and in control patients. Patients with the sleep apnoea syndrome confirmed polygraphically showed elevated levels of cyclic AMP and 5-HIAA. Cyclic AMP levels were inversely correlated with arterial Po(2), measured under resting conditions. The level of HVA also was raised, but the change was not statistically significant.

Cyclic AMP↗

Urinary excretion of catecholamines and metabolites in the Lyon strain of genetic hypertensive rats.

Urinary catecholamines (Norepinephrine : NE, Epinephrine : E) methoxylated amines (Metanephrine : MN, Normetanephrine : NMN) and 3-methoxy-4-hydroxyphenylglycol (MHPG) have been studied in the Lyon hypertensive strain of rats (LHS) and their normotensive controls (LNS) at three ages (5, 9 and 21 weeks) characteristic of the development of hypertension. In 5-week-old rats, increased excretion of E, MN, NMN and early elevation of the ratio E/E+NE were observed, thus suggesting a sympatho-adrenal hyperactivity, with accelerated maturation of E secretion. At adult age, the excretion of most adrenergic metabolites was similar in the two strains of rats. However, the data from adult LHS are difficult to interpret because of a potential renal impairment at this age. Furthermore, there was a positive correlation between systolic blood pressure and urinary catecholamines at 5 weeks and 9 weeks of age but not at 21 weeks. It is suggested that the early sympathoadrenal hyperactivity, which disappears with age, may be related to the onset of hypertension in the Lyon strain of hypertensive rats.

Adrenal Glands↗

Serotoninergic dysfunction in the 47, XYY syndrome.

In six XYY patients suffering from aggressiveness and admitted by order of law into a security setting for acts of violence, the estimation of cerebrospinal fluid amine metabolites before and after a probenecid test revealed a clear decrease in the turnover of central serotonin (5-HT) while that of dopamine (DA) was unchanged. The treatment with the 5-HT precursor, L-5-hydroxytryptophan (L-5-HTP), in five of the XYYs resulted in a clinical status equivalent to that observed when the patients were previously treated by conventional neuroleptics.

5-Hydroxytryptophan↗

Dihydralazine and catecholamine-synthesizing enzymes in spontaneous hypertension.

Dihydralazine treatment which lowered blood pressure in young rats from the Lyon Hypertensive Strain (LHS), did not change phenylethanolamine-N-methyltransferase (PNMT) activity, but decreased tyrosine hydroxylase and dopamine-beta-hydroxylase activities in the C2 medullary region. These data suggest that the increase in PNMT activity, previously described for this strain, is not a consequence of the developing hypertension and that hypotensive treatment could inactivate some catecholaminergic neurons of the medulla oblongata.

Adrenal Medulla↗

Distribution of adrenaline-synthesizing enzyme activity in the human brain.

A study of the distribution of phenylethanolamine-N-methyl-transferase (PNMT) activity in normal human brain is presented. After a preliminary dissection to separate brain tissue for formalin fixation and tissue designed for biochemical studies, the hemi-brain stem is cut in slices by hand and a cerebral hemisphere is cut on a cyromicrotome. "Punches" are made with an operating microscope. The dissection method was used to study the distribution of PNMT activity in 117 "punches" made on 21 slices obtained from 5 normal human brains. The caudo-rostral distribution of PNMT activity in C1 and C2 groups was found to be identical in each brain. The distribution of PNMT activity was found to be similar to that in the rat, but, in addition, important activity was found in the substantia nigra, internal pallidium and nucleus accumbens.

Brain↗