Biomedical subjects

J Sacquet

Publications and source records attributed to J Sacquet.

17 recordsLinked to original sources

PubMed2006

Long-term fate and distribution of newborn cells in the adult mouse olfactory bulb: Influences of olfactory deprivation.

The adult subventricular zone produces neuroblasts that migrate to the main olfactory bulb, where they differentiate into interneurons in the glomerular and granular layers. Using bromodeoxyuridine labeling, the survival of newborn cells was assessed in these two layers of the MOB in control mice and in mice unilaterally deprived from sensory input by naris occlusion. In control main olfactory bulbs, bromodeoxyuridine-positive cell density decreased about 70% between 15 and 180 days post-bromodeoxyuridine administration but earlier in the glomerular layer than in the granular layer. At all time points examined, newborn cell density was higher in the deep granular layer than in the superficial granular layer. Occlusion started at the age of 2 months and lasted for 15, 30, 45, 60 or 180 days. The newborn cell survival was similarly reduced in both layers by occlusion, during a critical period 15 and 45 days post-occlusion. Interestingly, olfactory deprivation decreased bromodeoxyuridine-positive cell density in the deep granular layer only, indicating a greater dependence of cell fate on sensory input in this sub-layer. Neuronal differentiation was assessed in the granular layer and glomerular layer by multiple double-labeling 45 days post-bromodeoxyuridine-injections, the time point at which the proportion of bromodeoxyuridine-positive cells expressing a neuronal marker reached approximately 85% in the granular layer and approximately 50% in the glomerular layer. Naris occlusion did not significantly affect these proportions. Taken together, our results reveal that the survival of newborn cells has a different time course in the glomerular layer and in the granular layer, but is similarly decreased in each layer by olfactory deprivation. In addition, our data suggest a functional heterogeneity of neurogenesis within the granular layer.

Analysis of Variance↗

PubMed2000

Cyclooxygenases 1 and 2 and thromboxane synthase in kidneys of Lyon hypertensive rats.

Compared with their two normotensive (LN and LL) controls, genetically hypertensive rats of the Lyon strain (LH) exhibit increased renal vascular resistance and a blunted pressure natriuresis function as well as an increased urinary excretion of vasoconstrictor prostanoids. The aim of this study was to assess in the kidneys of these animals the synthesis of vasoconstrictor or sodium-retaining prostanoids. The relative abundance of the mRNAs of cyclooxygenases (COX) 1 and 2 and of thromboxane A2 synthase (TXS), was measured by reverse-transcription polymerase chain reaction (RT-PCR) in renal cortex and medulla dissected in groups of male LH, LN, and LL rats either in baseline conditions or after 1 week of salt loading (1.5% NaCl in the drinking water). In basal conditions, at 3 and 11 weeks of age COX1 was expressed in the kidneys of all rats more markedly in medulla than in cortex. COX2 was poorly expressed in the whole kidney. TXS expression was usually too low to be quantified. No difference could be observed among LH, LN, and LL rats. After salt loading, the expression of COX1 was enhanced in the medulla and that of COX2 reduced in the cortex. LH rats differed from controls by a significantly more marked increase in medullary COX1 expression. The present work excludes any primary generalized increase in the renal expression of the genes that control the synthesis of vasoconstrictor prostanoids in LH rats, but suggests that medullary COX1 is upregulated by salt in these animals.

Animals↗

PubMed1994

Thromboxane A2-prostaglandin H2 and renovascular hypertension in rats.

To evaluate the contribution of thromboxane (Tx) A2-prostaglandin (PG) H2 in two-kidney, one-clip Goldblatt hypertension (GH), 26 GH rats were chronically treated (GHT) with a specific TxA2-PGH2 receptor antagonist, CGS-22652 (30 mg.kg-1.24 h-1 sc); 28 others as well as 17 sham-clipped (SC) rats received vehicle. Twelve GH and 3 GHT rats developed malignant hypertension and died. After 6 wk of treatment, GH rats exhibited higher mean blood pressure (BP; 189 +/- 3 vs. 118 +/- 2 mmHg) and an increased vascular reactivity to the main pressor agents compared with SC rats. Chronic TxA2-PGH2 receptor blockade lowered mean BP in 13 GHT rats (125 +/- 3 mmHg) and decreased their vascular reactivity compared with GH rats. However, 10 GHT rats remained hypertensive (190 +/- 9 mmHg) and differed from the former by an increased vascular reactivity to vasopressin. It is concluded that renal artery clipping induces either benign or malignant hypertension. In benign forms, TxA2-PGH2 blockade normalizes BP through decreasing the vascular responsiveness to the main pressor agents. In malignant forms, it limits the elevation of BP and markedly reduces mortality.

Aging↗

PubMed1993

Do thymic-neuroendocrine interactions play a role in the antihypertensive effect of neonatal thymectomy in Lyon hypertensive rats?

Previous studies showed that neonatal thymectomy prevented the spontaneous increase in blood pressure in genetically hypertensive rats (LH) of the Lyon strain, leaving untouched that of their normotensive controls (LN). As the thymus is connected to the neuroendocrine system through secretion of hormonal factors, we investigated the possible role played by these factors in hypertension of LH rats. To that end we studied, in sham-operated and neonatally thymectomized LH rats, the blood pressure effects of thymostimulin, a partially purified thymus extract and examined whether changes in major neuroendocrine factors of blood pressure regulation occurred in thymectomized LH rats. Thymostimulin (1 or 10 mg/kg/48 h) did not modify blood pressure in sham-operated LH rats and failed to consistently increase it in neonatally thymectomized animals. Urinary mineralocorticoids, catecholamines and their metabolites, and plasma renin levels were not altered by neonatal thymectomy. Plasma testosterone was decreased to a similar degree by neonatal thymectomy in LH and normotensive controls. These results do not favor a pressor role of thymic hormonal factors in LH rats and show that the antihypertensive effect of neonatal thymectomy is not secondary to a decreased secretion of catecholamines, renin, mineralocorticoids, and testosterone. They therefore suggest that the role of the thymus in genetically hypertensive LH rats is more likely mediated by cellular immune mechanisms than by hormonal processes.

Animals↗

PubMed1993

Effects of naftidrofuryl on isolated perfused kidneys of spontaneously hypertensive rats.

1. Experiments were designed to determine the effects of low concentrations (5-500 nmol/L) of naftidrofuryl, a 5-hydroxytryptamine (5-HT) antagonist, on renal functions and prostanoid synthesis responses to noradrenaline (NA) and 5-HT. Isolated kidneys of 8 week old male spontaneously hypertensive rats were perfused at a constant flow rate in a single-pass system. 2. In baseline conditions, naftidrofuryl did not modify the renal vascular resistance and the glomerular filtration rate (GFR), although it elicited a significant but not dose-dependent increase in the venous excretion of 6-keto-prostaglandin (PG) F1 alpha and thromboxane (Tx)B2, the stable end-products of PGI2 and TxA2, respectively. 3. NA increased renal vascular resistance and GFR in a dose-dependent manner and enhanced the venous excretion of 6-keto-PGF1 alpha and TxB2. Naftidrofuryl significantly attenuated the effects of NA on renal vascular resistance, abolished those on GFR and enhanced, at the highest concentration (500 nmol/L) only, those on 6-keto-PGF1 alpha excretion. 4. 5-HT increased renal vascular resistance but not GFR. It did not change the sodium excretion and the release of 6-keto-PGF1 alpha and TxB2. Naftidrofuryl blunted the RVR response to 5-HT without change in the prostanoid release. The inhibitory action of naftidrofuryl was not modified by indomethacin which, by itself, prevented the vasoconstrictor response to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

PubMed1993

Blood pressure effects of thromboxane A2 blockade in spontaneously hypertensive rats.

1. The effects of CGS 22652, a thromboxane (Tx) A2 synthase inhibitor and TxA2/prostaglandin (PG) H2 receptor antagonist, on blood pressure (BP) were studied in conscious freely moving spontaneously hypertensive rats (SHR). 2. Three groups of 13 male SHR were subcutaneously infused from 5 to 11 weeks of age via osmotic minipumps with CGS 22652 at doses of 5 (SHRa) or 10 (SHRb) mg/kg per 24 h or with the vehicle only (SHRc). A fourth group (SHRd, n = 13) was orally treated from 3 to 11 weeks of age with CGS 22652 (30 mg/kg) given by gavage once a day. 3. CGS 22652 dose-dependently reduced the age-related increase in systolic BP. The pressor response to noradrenaline (200 ng/kg, i.v.) but not to angiotensin I or II was slightly (P < 0.05) diminished in 11 week old SHRb and SHRd compared to SHRc. Acute ganglionic blockade by trimethaphan (10 mg/kg, i.v.), as well as angiotensin converting enzyme inhibition by perindopril (2 mg/kg, i.v.) decreased BP to a similar extent in the four groups. After combined blockade of vasopressin receptors and of the autonomic nervous system and the administration of a direct vasodilator (hydralazine, 3 mg/kg, i.v.), the residual mean BP was identical in the four groups of rats. 4. Chronic treatment with CGS 22652 dose-dependent antagonized the TxA2/PGH2 receptors but did not modify the TxA2 synthesis. The urinary sodium excretion did not differ between groups. 5. In conclusion, at the doses used, CGS 22652 given either orally or subcutaneously exhibited only TxA2/PGH2 receptor blocking properties in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1992

Cardiovascular habituation to emotional stress in Lyon hypertensive rats.

1. Intra-aortic blood pressure was recorded continuously in freely moving genetically hypertensive (LH), normotensive (LN) and low blood pressure (LL) rats of the Lyon strain during two 11 h periods (08:00-19:00 h). During the first period (control), the animals were left undisturbed and during the second period (stress), a jet of air was applied for 20 min every hour. Urine was collected simultaneously and analysed for its content in norepinephrine and epinephrine. 2. The first exposure to the stressor induced larger increases in blood pressure and heart rate in LH than in LN and LL rats. However blood pressure and heart rate responses to the 10 following stressors decreased in LH rats while they remained stable in LN and LL animals. 3. Repeated stress exposure induced significant increases in epinephrine excretion in both LN and LL but not in LH rats. 4. It is concluded that LH rats exhibit marked cardiovascular habituation to repeated stress. Taken together with the lack of stress-induced sympathoadrenal activation, this suggests a reduced level of emotional responsiveness in Lyon hypertensive rats.

Adrenal Medulla↗

PubMed1988

NE turnover in genetically hypertensive rats of Lyon strain. I. Brain nuclei.

Several indirect evidences of alterations in the central catecholaminergic structures were obtained in genetically hypertensive rats. Because they could be of pathogenetic value, we measured, in the present work, the in vivo turnover (TO) of norepinephrine (NE) in brain areas of 5- and 22-wk-old genetically hypertensive (LH) rats of the Lyon strain, and their simultaneously selected normotensive (LN) and low blood pressure (LL) controls. Among the changes observed, the increased TO of NE in the A2 and A6 regions of 5-wk-old LH rats and its decrease in the posteroventral hypothalamic nucleus of 22-wk-old LH animals appeared likely to compensate for hypertension. On the contrary, the decreased TO of NE in the anterior hypothalamic nucleus observed at 5 wk and in the A6 and A1 areas at 22 wk of age in LH rats could participate in the development or the maintenance of hypertension. Above all, it was postulated that the increased TO of NE found in the A7 region of 5-wk-old LH rats could play a primary role in the pathogenesis of hypertension in the Lyon model.

Aging↗

PubMed1988

NE turnover in genetically hypertensive rats of Lyon strain. II. Peripheral organs.

The peripheral sympathetic nervous system (SNS) is a major determinant of blood pressure and is likely to be involved in the pathophysiology of hypertension. Because SNS activity varies among organs, we measured the in vivo turnover (TO) of norepinephrine (NE) in seven organs of 5- and 22-wk-old genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) rats of the Lyon strains. The TO of NE was found normal in the superior cervical ganglia and decreased in the heart of 5-wk-old LH rats compared with both LL and LN controls. This suggests that sympathetic cardiac innervation may not be involved in the development of hypertension. On the contrary, an increased TO of NE in the kidney cortex and an elevated TO of dopamine associated with an increased epinephrine content in the adrenal medulla were observed in 5-wk-old LH rats, which could participate in the development of hypertension in the Lyon model.

Adrenal Medulla↗

PubMed1988

Brain and peripheral noradrenergic neuron activity in developing genetically hypertensive rats of the Lyon strain.

In order to estimate the alterations in the activity of noradrenergic brain areas and peripheral nerves in relation to genetic hypertension, the concentration and the in-vivo turnover (TO) of norepinephrine (NE) were measured in various brain and peripheral structures of 5 and 22 week-old genetically hypertensive (LH), normotensive (LN) and low blood pressure (LL) male rats of the Lyon strains. LH rats significantly differed from both LN and LL age-matched controls by: i) at 5 weeks, a lowered TO of NE in the anterior hypothalamic region and the median eminence; an elevated TO of NE in the A6 and A7 areas, and in the kidney cortex, and an elevated TO of dopamine in the adrenal medulla, ii) at 22 weeks, a decreased TO of NE in A1 and A6 regions and an increased TO of NE in the thoracic spinal cord. These data suggest that an increased activity of the renal nerves and of the adrenal medulla, possibly originating in central alterations of noradrenergic neurons, could be involved in the development of hypertension in the Lyon strain.

Animals↗

PubMed1988

Liquid-chromatographic determination of free and total 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol in urine.

We describe the conjoint measurement in urine of the alcoholic catecholamine metabolites 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG). The method involves extraction with ethyl acetate and back-extraction into acetic acid (MHPG), followed by adsorption onto alumina (DHPG). The separation is performed by reversed-phase liquid chromatography with column switching and amperometric detection. Total (free plus conjugated) compounds are determined after a 24-h enzymatic hydrolysis. Twelve-hour excretion values for normal and hypertensive subjects are given, together with results obtained for patients with pheochromocytoma, chemodectoma, and congenital dopamine-beta-hydroxylase deficiency. The assay is sensitive, reproducible, and free of interferences, and may lead to a better understanding of overall catecholamine metabolism in health and disease.

Adrenal Gland Neoplasms↗

PubMed1985

Catecholamine concentrations in discrete brain nuclei and sympathetic tissues of genetically hypertensive mice.

Catecholamine concentrations were determined at central and peripheral level in high blood pressure (HBP), low blood pressure (LBP) and random bred (RB) mice. In HBP mice compared to LBP, the noradrenaline concentration was lower in the locus coeruleus, medullary A1-C1 and A2-C2 areas, thoracic spinal cord, posteroventral hypothalamus and nucleus hypothalamicus anterior, while dopamine concentration was decreased in the striatum. Adrenal catecholamine levels were higher in both HBP and LBP compared to RB mice.

Adrenal Medulla↗

PubMed1985

Brain, spinal cord and adrenal catecholamine concentrations in neonate rats of the Lyon hypertensive strain.

The catecholamine concentrations were determined in brain parts, spinal cord and adrenals of neonate hypertensive rats of the Lyon strain (LH), compared to normotensive (LN) and low-blood-pressure (LL) control rats. In adrenals of LH rats, noradrenaline and adrenaline concentrations are increased, and 3,4-dihydroxyphenylacetic acid (DOPAC) concentration decreased. At the central level, the DOPAC concentration and the ratio DOPAC/dopamine are decreased in the mesencephalon and the forebrain of LH rats. These results suggest that neonate LH rats exhibit a decreased activity in central dopaminergic neurons, and an enhanced maturation of the adrenals.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1985

[Central and peripheral catecholamines in the genetically hypertensive mouse].

The aim of this work was to assess if biochemical alterations are present in catecholaminergic neurons of genetically hypertensive mice (HBP strain) compared to genetically hypotensive mice (LBP strain), as well as to mice of the population (R) from which HBP and LBP strains have been selected. For that purpose, dopamine (DA), noradrenaline (NA) and adrenaline (A) concentrations were determined by high performance liquid chromatography with electrochemical detection, in peripheral structures and brain nuclei of adult male mice from these three strains. In the adrenal medulla of HBP mice, DA, NA and A concentrations are increased when compared to R, but not to LBP mice. In the superior cervical ganglia of HBP mice, the NA concentration is decreased when compared to LBP, but increased when compared to R mice. At the central level, the NA concentration is decreased in HBP mice when compared to LBP, but not significantly changed when compared to R mice, in the following regions: locus coeruleus (-39 p. 100, p less than 0.001), A1-C1 (-17 p. 100, p less than 0.001) and A2-C2 (-19 p. 100, p less than 0.001) areas of the medulla oblongata, thoracic spinal cord (-26 p. 100, p less than 0.01), posteroventral hypothalamus (-18 p. 100, p less than 0.01) and nucleus hypothalamicus anterior (-14 p. 100, p less than 0.01). In the nucleus periventricularis, NA concentration of HBP mice is not changed when compared to both LBP and R animals. Finally, in the caudate nucleus of HBP mice, the DA concentration is decreased when compared to both R and LBP mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

PubMed1984

Central and peripheral catecholamine synthesizing enzymes during the development of two-kidney, one clip hypertension in rats.

The activities of the catecholamine synthesizing enzymes have been determined in discrete brain areas and in peripheral tissues of rats, at different times after clipping the left renal artery (two-kidney Goldblatt hypertension, 2KGH) and in sham operated animals. Three days after clipping the only enzymatic change was a slight decrease in plasma dopamine-beta-hydroxylase (DBH) activity. Ten days after clipping no change in enzymatic activity was found at the central level. However, the DBH and the phenylethanolamine-N-methyltransferase (PNMT) activities were increased in the adrenal medulla (+49.0%, P less than 0.001 and +36.6%, P less than 0.001, respectively) and DBH activity was also increased in the superior cervical ganglia (+22.8%, P less than 0.01). These data suggest that sympathetic hyperactivity is present in 2KGH rats when hypertension is established. In addition, as this type of hypertension does not alter the PNMT activity in brainstem areas, it seems that the alterations in PNMT activity reported for genetically hypertensive rats are unlikely to be secondary to the elevated blood pressure.

Adrenal Medulla↗

PubMed1982

[Vascular reactivity in young genetically hypertensive rats of the Lyons strain].

The vascular sensitivity to noradrenaline (NA), phenylephrine (PE) and angiotensin II (AII) has been studied in 8 week-old male rats of the genetically hypertensive (LH) and normotensive (LN) Lyon strains. Vascular sensitivity was obtained from the blood pressure response-curves observed in urethane anesthetized rats having received ganglioplegics and atropine. A cocaine pretreatment allowed to assess the influence of a reuptake blockade on the responses to NA. The vascular sensitivity of NA, PE and AII was normal in LH rats, while the cocaine blocked reuptake process was less important in LH than in LN rats. When comparing these results to those, previously obtained on the activity of the sympathetic nervous system, it appeared that: in the young prehypertensive LH rat an increased sympathetic activity was associated with a normal vascular reactivity to NA. On the contrary, in old LH rats, with established hypertension, the sympathetic activity returned to normal while a vascular hypersensitivity to NA developed. Therefore it is concluded that the overall efficacy of the sympathetic nervous system is increased at all stages of the development of genetic hypertension in the Lyon strain.

Angiotensin II↗

PubMed1979

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↗