bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renal Hemodynamics in Young and Old Spontaneously Hypertensive Rats during Intrarenal Infusion of Arginine Vasopressin
Authors: Christiansen Rolf E.F. , Roald Anca B. , Gjerstad Camilla , Tenstad Olav , Iversen Bjarne M. 
Published: April 2003

<i>Background/Aims:</i> To gain insight into the effect of arginine vasopressin (AVP) on renal hemodynamics in hypertensive rats, we investigated the vasoconstrictive response to AVP on total renal blood flow (RBF) and total and zonal glomerular filtration rate (GFR) in young and old spontaneously hypertensive rats (SHR). A hypothesis of increased AVP sensitivity in the juxtamedullary cortex of SHR was tested. <i>Methods:</i> Total RBF and total and zonal GFR were studied in 10- and 40-week-old SHR and normotensive Wistar-Kyoto rats (WKY). RBF was recorded by a flowmeter before infusion of AVP and immediately after injection of a bolus dose of 10 ng AVP. Whole kidney GFR and its intracortical distribution was measured by the tubular uptake of <sup>125</sup>I- and <sup>131</sup>I-labelled aprotinin before and during a continuous infusion of AVP 5 ng/min. Ligand binding measurements of preglomerular V<sub>1a</sub> receptors were performed in young and old rats. <i>Results:</i> RBF decreased by 43 ± 3% in 10-week SHR (9.2 ± 0.5 vs. 5.2 ± 0.3 ml·min<sup>–1</sup>·g<sup>–1</sup>), significantly more than 10-week WKY where RBF decreased by 35 ± 3% (9.6 ± 0.7 vs. 6.5 ± 0.5 ml·min<sup>–1</sup>·g<sup>–1</sup>) (p < 0.05). The effect of AVP on RBF was attenuated in 40-week-old rats where the decline in RBF was 29 ± 5% in SHR and 23 ± 4% in WKY (p > 0.05). GFR decreased by 6 ± 3% (1.03 ± 0.04 vs. 0.96 ± 0.04 ml·min<sup>–1</sup>·g<sup>–1</sup>, p < 0.05) in 10-week SHR and was unchanged in 10-week WKY (1.10 ± 0.07 vs. 1.08 ± 0.04 ml·min<sup>–1</sup>·g<sup>–1</sup>, p > 0.10). GFR decreased by 11 ± 10% in 40-week SHR and by 4 ± 4% in 40-week WKY (p > 0.05). AVP infusion significantly increased filtration fraction in all groups except 40-week SHR, indicating that AVP has the strongest vasoconstrictive effect on postglomerular vessels. The intrarenal distribution of GFR was unchanged in the normotensive and hypertensive groups. V<sub>1a</sub> receptor density was upregulated in young SHR compared to young WKY (p < 0.05), but downregulated in old compared to young SHR (p = 0.05). <i>Conclusion:</i> The results indicate that AVP sensitivity is not increased in the juxtamedullary cortex in SHR and the reduced vasoconstrictive effect in old SHR is due to a reduced density of V<sub>1a</sub> receptors.
Chronic Melatonin Treatment Counteracts Glucocorticoid-Induced Dysregulation of the Hypothalamic-Pituitary-Adrenal Axis in the Rat
Authors: Konakchieva Rossitza , Mitev Yuri , Almeida Osborne F.X. , Patchev Vladimir K. 
Published: April 2003

Transient exposure of rats to high doses of dexamethasone (DEX; 500 µg/day for 5 days) produced a host of symptoms that are indicative of hypothalamic-pituitary-adrenal (HPA) axis dysregulation, such as increased adrenocortical secretion over 24 h, blunted and prolonged secretory response to emotional stress, refractoriness of adrenocorticotropin in vitro release to stimulation with the secretagogues corticotropin-releasing hormone (CRH) and vasopressin, decreased levels of mRNA encoding type II corticosteroid receptors in the hippocampus and increased numbers of transcripts encoding CRH in the paraventricular nucleus. Daily administration of melatonin (MEL; 80 µg/kg) concomitantly with, and for 5 days after discontinuation of, glucocorticoid treatment ‘normalized’ most of the symptoms of impaired HPA regulation caused by the exposure to DEX. While none of the treatments used caused major shifts in circadian patterns of corticosterone secretion, MEL administration was associated with diminished overall corticosterone secretion and increased sensitivity to glucocorticoid feedback. Taken together, these findings indicate that chronic MEL treatment may protect several regulatory components of the HPA axis from glucocorticoid-induced deterioration.
Effect of Glutamate Receptor Agonists on Catecholamine Secretion in Bovine Chromaffin Cells
Authors: González María Pilar , Herrero María Teresa , Vicente Susana , Oset-Gasque María Jesús 
Published: April 2003

In this study, the effects of glutamate and glutamate receptor agonists in cultured chromaffin cells from bovine adrenal medulla were investigated. It was found that glutamate increases basal catecholamine (CA) secretion in a dose-dependent manner. This effect is mimicked by specific agonists of the four known glutamate receptors N-methyl-<i>D</i>-aspartate (NMDA), quisqualate/(RS)-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate (KA), and trans-(+)-1-amino-1,3-cyclopentane dicarboxylic acid (t-ACPD), which increased both basal and nicotine-evoked CA secretion. The NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid, 6-cyano-7-nitroquinoxaline-2,3-dione, an antagonist of KA and AMPA receptors, and <i>L</i>-(+)-2-amino-3-phosphonopropionic acid, an antagonist of the t-ACPD receptor, inhibited the stimulatory effect of related glutamate agonists. Hexamethonium, an antagonist of the nicotinic receptor, failed to influence glutamate agonists except for a 15% inhibition of KA. The increase in CA secretion produced by a 100 µ<i>M</i> concentration of glutamate agonists was about 20–60% of that obtained with 10 µ<i>M</i> of nicotine, an agonist of the physiological stimulatory cholinergic receptor. The increase in CA secretion produced by glutamate was accompanied by both an increase in bisoxonol fluorescence, suggesting membrane depolarization, and by an increase in intracellular Ca<sup>2+</sup> concentrations. Results obtained with image analysis on single cells indicated that the percentage of cells which respond to the stimulation of 50 µ<i>M</i> of glutamate is 42%. From these results, we conclude that glutamate, through its four known glutamate receptors, can increase both basal and nicotine-evoked CA secretion in chromaffin cells by a process which involves membrane depolarization and an increase in intracellular calcium levels.
Increase of Gonadotropin-Releasing Hormone Concentration in Pituitary Portal Blood after Substance P Administration in Male Rats
Authors: Walczewska Anna , Szkudlarek Urszula , Jakubowska-Naziemblo Barbara , Dziedzic Barbara , Traczyk Wladyslaw Z. 
Published: April 2003

Substance P (SP) affects gonadotropin release from the anterior pituitary gland. In the present study we tested whether SP exerts this effect through GnRH release into pituitary portal blood in intact male rats (INT), orchidectomized rats with s.c. chronically implanted empty Silastic capsule (ORCX), testosterone capsule (ORCX + T), and 17β-estradiol capsule (ORCX + E<sub>2</sub>). The pituitary glands were exposed by the transpharyngeal approach under urethane-chloralose anesthesia. Then, the stalk portal vessels were cut and three 30-min portal blood samples were collected. Each first sample of blood was treated as a control before 0.2 ml injection of normal saline, 5 µg, or 25 µg of SP in 0.2 ml of normal saline into the internal carotid artery. GnRH concentration in the purified portal plasma were measured by RIA. Injection of SP into the internal carotid artery caused a significant increase in GnRH concentration in pituitary portal plasma only in INT rats. The higher dose of SP markedly increased GnRH concentration in the 1st blood sample (p < 0.001) and in the 2nd blood sample GnRH concentration was lower but still significant higher than prior SP injection (p < 0.05). The lower dose of SP increased GnRH concentration later, only in the 2nd portal blood sample after intracarotid SP injection (p < 0.001). Injection of normal saline had no effect on GnRH concentration in pituitary portal blood in INT rats. In ORCX, ORCX testosterone- and estrogen-implanted rats portal plasma GnRH concentrations were not changed significantly after injection of both doses of SP. These results indicate that SP stimulates GnRH release into pituitary portal blood and the influence of SP on GnRH neurons depends on the levels of circulating gonadal steroid hormones.
Effects of Dexamethasone and Alprazolam, a Benzodiazepine, on the Stimulatory Effect of Hexarelin, a Synthetic GHRP, on ACTH, Cortisol and GH Secretion in Humans
Authors: Arvat Emanuela , Maccagno Barbara , Ramunni Josefina , Di Vito Lidia , Gianotti Laura , Broglio Fabio , Benso Andrea , Deghenghi Romano , Camanni Franco , Ghigo Ezio 
Published: April 2003

Hexarelin (HEX) is a synthetic GHRP which acts on specific receptors at both the pituitary and the hypothalamic level to stimulate GH release both in animals and in humans. Like other GHRPs, HEX possesses also acute ACTH and cortisol-releasing activity similar to that of hCRH. The mechanisms underlying the stimulatory effect of GHRPs on hypothalamo-pituitary-adrenal (HPA) axis are still unclear, although a CNS-mediated action has been demonstrated. In 6 normal healthy young women (26–34 years) we studied the effects on ACTH and cortisol secretion of HEX (2.0 µg/kg i.v. at 0 min) alone and preceded by dexamethasone (DEXA, 1 mg p.o. at 23.00 h on the previous night) or alprazolam (ALP, 0.02 mg/kg p.o. at –90 min), a benzodiazepine which binds to GABA receptors and possesses CRH-mediated inhibitory activity on HPA axis. ACTH and cortisol secretion after saline administration as well as the GH response to HEX alone and preceded by DEXA or ALP were also studied. HEX administration elicited an increase in ACTH (peak vs. baseline, mean ± SEM: 28.0 ± 6.7 vs. 11.7 ± 2.2 pg/ml, p < 0.05) and cortisol secretion (162.6 ± 15.0 vs. 137.7 ± 12.6 µg/l, p < 0.05). DEXA pretreatment strongly inhibited basal ACTH (3.2 ± 0.7 pg/ml, p < 0.01) and cortisol levels (11.3 ± 2.5 µg/l, p < 0.001) and abolished the ACTH and cortisol responses to HEX (3.6 ± 0.9 pg/ml, p < 0.01 and 10.7 ± 2.0 µg/l, p < 0.001), respectively. On the other hand, ALP pretreatment did not significantly modify basal ACTH (7.9 ± 2.0 pg/ml) and cortisol levels (127.6 ± 14.5 µg/l) but abolished the HEX-induced ACTH and cortisol secretions (8.6 ± 2.4 pg/ml, p < 0.05 and 111.0 ± 6.0 µg/l, p < 0.05), respectively. ACTH and cortisol levels after HEX when preceded by ALP overlapped with those recorded during saline. HEX induced a clear GH response (peak at 15 min vs. baseline: 65.5 ± 20.5 vs. 2.2 ± 0.7 µg/l, p < 0.03) which was blunted by ALP (peak at 15 min: 21.5 ± 5.5 µg/l, p < 0.05) while it was not modified by DEXA pretreatment (78.7 ± 7.6 µg/l). In conclusion, our present data demonstrate that the ACTH- and cortisol-releasing effect of HEX is abolished by either dexamethasone or alprazolam, a benzodiazepine, which is even able to blunt the GH-releasing activity of the hexapeptide. These findings suggest that, in physiological conditions, the stimulatory effect of GHRPs on HPA axis is sensitive to the negative glucocorticoid feedback and could be mediated by GABAergic mechanisms; the latter seem also involved in the GH-releasing activity of GHRPs.
Increased Expression of Magnocellular Vasopressin mRNA in Rats with Deoxycorticosterone-Acetate Induced Salt Appetite
Authors: Grillo Claudia A. , Saravia Flavia , Ferrini Monica , Piroli Gerardo , Roig Paulina , García Silvia I. , de Kloet E. Ronald , De Nicola Alejandro F. 
Published: April 2003

The neuropeptides arginine vasopressin (AVP) and oxytocin (OT) have been implicated in the genesis of hypertension due to deoxycorticosterone acetate (DOCA)-salt treatment of uninephrectomized rats. In this work, we studied if DOCA treatment of intact rats in doses arousing a salt appetite (a prehypertensive state), modulated mRNA for AVP and OT in the hypothalamus. Male Sprague-Dawley rats were offered both tap water and 3% NaCl in separate bottles and received vehicle or subcutaneous injections of 10 mg DOCA on alternate days for 7 days (4 injections) or 17 days (9 injections). They developed a preference for 3% NaCl solutions 24–48 h after treatment. Brain slices from rats killed on the 8th or 18th day were exposed to <sup>35</sup>S-labeled probes encoding prepro-AVP mRNA or OT mRNA, respectively. Expression of these mRNAs was measured in the magnocellular and parvocellular divisions of the paraventricular nucleus (PVN) and magnocellular cells of the supraoptic nucleus (SON). No changes were obtained in neuropeptide mRNA levels in the parvocellular division of the PVN between control and the two groups of DOCA-treated rats. However, DOCA-treated animals presented an increased number of grains per cell for AVP mRNA in the magnocellular division of the PVN and in magnocellular cells of the SON, as shown by group mean comparisons and frequency histograms. No changes were detected for OT mRNA. In a second series of studies, control or DOCA-treated rats were offered 3% NaCl or water as the only choice. Animals drinking 3% NaCl showed increased AVP and OT mRNA levels, whether they received DOCA or not. However, AVP mRNA levels in both nuclei were higher in DOCA-treated rats drinking 3% NaCl than in controls drinking salt solution. In comparison, control and DOCA-treated rats drinking water showed lower levels of AVP mRNA. OT mRNA levels in the SON remained unchanged in the same groups. The results suggest that in the magnocellular cells of the PVN and SON, increments in AVP mRNA are obtained following increments in salt intake produced by either mineralocorticoid treatment or exclusive salt drinking. In rats offered salt solution and water to drink, DOCA effects on AVP mRNA developed before changes occurred in serum sodium levels. Because combined DOCA + salt treatment induced a higher response in terms of AVP mRNA expression, we suggest that AVP could be a target of the central effects of the mineralocorticoid.
Estrogenic Stimulation of Hypothalamic-Limbic System Metabolism in Ageing Diabetic C57BL/KsJ Mice
Authors: Garris David R. 
Published: April 2003

The therapeutic influences of estrogen treatment on age- and diabetes-related declines in regional brain glucose utilization (RBGU) rates were evaluated in 8- to 20-week-old female C57BL/KsJ normal <i>(+/?)</i> and diabetic <i>(db/db)</i> mice. Following either oil vehicle (oil: 0.1 ml) or estradiol (E: 1 µg/3.5 days) treatments starting at 3 weeks of age, RBGU rates were subsequently determined at 8, 12, 16 and 20 weeks of age. A gradual decline in the basal rate of brain glucose utilization was observed in all control (oil- and E-treated) groups between 8 and 20 weeks. Expression of the hyperglycemic-obese diabetes syndrome in <i>db/db</i> mice resulted in a significant reduction in RBGU rates between 8 and 20 weeks relative to control values. In estrogen-sensitive hypothalamic, septal and amygdaloid regions, E therapy modulated RBGU rates in <i>db/db</i> mice relative to oil-treated diabetics, but did not significantly alter utilization rates in <i>+/?</i> mice. In cortical samples, E therapy had no significant influence on glucose utilization rates in either control or diabetic groups. A noticeable pattern of maturation-associated decline in CNS glucose utilization rates in all brain regions resulted in comparable regional metabolic indices being exhibited by all groups at 20 weeks of age, with the exception of the diabetes-associated exacerbation of RBGU rates in the oil-treated <i>db/db</i> group. These data demonstrate that the normal development-related decline in regional brain carbohydrate metabolism is accelerated by the diabetes syndrome, and that E therapy can modulate the syndrome-associated suppression of glucose utilization in steroid-sensitive CNS loci. These data suggest that the depressive influences of the diabetes syndrome on brain carbohydrate utilization rates may be therapeutically modified in recognized CNS regions possessing steroid-sequestering, metabolically responsive neurons.
Neuroendocrine Secretory Protein 55 (NESP55): Alternative Splicing onto Transcripts of the GNAS Gene and Posttranslational Processing of a Maternally Expressed Protein
Authors: Weiss Ulrike , Ischia Rudolph , Eder Susanne , Lovisetti-Scamihorn Paola , Bauer Richard , Fischer-Colbrie Reiner 
Published: April 2003

Recent studies established a novel genomically imprinted gene located 45 kb upstream of the human GNAS1 locus. This locus encoded for the Neuroendocrine Secretory Protein with an apparent molecular weight of 55,000 (NESP55), which is transcribed exclusively from the maternal allele. We sequenced rat and human NESP55 and investigated tissue-specific splicing of its mRNA and posttranslational modifications of the protein in various tissues. Alternative mRNA splicing of NESP55 was analyzed by sequencing of cDNA clones, RT-PCR and Northern blotting. Two main splice variants, which were generated in a tissue-specific manner, were identified: The open reading frame encoding NESP55 was spliced onto exons 2–13 of Gsα in the adrenal medulla, pituitary and the brain. In addition, in the pituitary a second shorter, prominent mRNA transcript was generated by splicing of NESP55 onto exons 2, 3 and N1 of Gsα. Several of the cDNA clones isolated contained inverted repeats of 50–150 bp at their 5′ or 3′ termini, which might form hairpin stems and thus alter mRNA stability. The NESP55 open reading frame encoded a hydrophilic protein of 28,018 Da (human) and 29,218 Da (rat), respectively, which resembled the class of acidic, neuroendocrine secretory proteins collectively called chromogranins. NESP55 is highly conserved among mammalian species. It is posttranslationally acidified by the addition of keratan sulfate glycosaminoglycan chains and differentially processed by endopeptidases in various endocrine and neuronal tissues.
Lesions of the Dorsomedial Hypothalamic Nucleus Do Not Influence the Daily Profile of Pineal Metabolism in Rats
Authors: Mota Sandra Regina , Canteras Newton Sabino , Bartol Ione , Skorupa Ana Lúcia , Scialfa Julieta Helena , Terra Ilza Mingarini , Afeche Solange Castro , Cipolla-Neto José 
Published: April 2003

The present study attempted to characterize the effects of electrolytic lesions of the hypothalamic dorsomedial nucleus on the daily profile of pineal metabolism as well as on the inhibition of pineal melatonin synthesis induced by acute light exposure during the night. Adult male Wistar rats (n = 107, 12:12 h light-dark cycle) were left intact (n = 47) or lesioned (n = 60). Lesioned rats and their respective controls were killed at six time points distributed throughout the light-dark cycle. At ZT (zeitgeber time) 18 the animals were killed either in the dark or after 15 min of light stimulation. Pineal glands were assayed using high-performance liquid chromatography with electrochemical detection (HPLC-ED). There was no difference in the amounts of pineal indoles between lesioned and control rats under any of the experimental situations tested. These results suggest that in rats, the hypothalamic dorsomedial nucleus does not participate in either the neural control of daily pineal metabolism or the nocturnal light-induced inhibition of the pineal metabolism.
Lactation Alters γ-Aminobutyric Acid Neuronal Activity in the Hypothalamus and Cerebral Cortex in the Rat
Authors: Kornblatt Joseph J. , Grattan David R. 
Published: April 2003

γ-Aminobutyric acid (GABA) neurons terminating in the hypothalamus have been implicated in the neuroendocrine regulation of reproductive hormones, particularly luteinizing hormone (LH) and prolactin. The aim of this study was to examine whether GABAergic neuronal activity in the hypothalamus was modified during lactation, and whether any observed changes correlated with changes in secretion of these hormones. Animals were divided into three experimental groups: diestrous controls, lactating with pups present (with pups), and lactating with pups removed for 4 h (without pups). Animals were decapitated either without treatment, or 60 min after inhibition of GABA degradation by aminooxyacetic acid (AOAA) (100 mg/kg, i.p.). The rate of GABA accumulation in the tissue after AOAA is a measure of GABA turnover. GABA turnover was estimated in 13 microdissected brain regions, and serum prolactin and LH measured by radioimmunoassay. Suckling was associated with significantly increased prolactin and significantly decreased LH compared with diestrous rats. In lactating rats with pups, GABA turnover was significantly increased in the cingulate cortex compared with diestrous rats. GABA turnover was significantly increased in the ventrolateral preoptic nucleus of lactating rats with pups compared with diestrous rats or lactating rats without pups. There was significantly lower GABA turnover in the anterior hypothalamic area, ventromedial and dorsomedial hypothalamic nuclei in lactating rats without pups compared with diestrous rats. There were no significant changes in other brain regions examined. The results demonstrate that activity of GABAergic neurons in specific parts of the hypothalamus and cerebral cortex is altered during lactation.
Glucocorticoid and Mineralocorticoid Receptors Are Involved in the Facilitation of Anxiety-Like Response Induced by Restraint
Authors: Calvo Nelson , Volosin Marta 
Published: April 2003

In previous studies, we have shown that male Wistar rats exposed to a single inescapable stressor session (15 min restraint) exhibited 24 h later an anxiogenic-like behavior in the elevated plus-maze (EPM), which was reversed by inhibition of corticosterone (CS) synthesis with metyrapone (75 mg/kg i.p.) 3 h before stress. Since CS binds to two central corticosteroid receptors, the mineralocorticoid (MR) and the glucocorticoid (GR) receptors, involvement of MR and GR in the modulation of anxiogenic responses was assessed in the EPM. Administration of the GR agonist dexamethasone (Dex, 1.25 µg/kg s.c.) to metyrapone-pretreated rats 1 h before restraint restored the anxiogenic-like response induced by the stressor. Removal of the adrenals also inhibited the anxiogenic-like effect, which was restored by either Dex (1.25 µg/kg s.c.), the MR agonist deoxycorticosterone (0.8 mg/kg s.c.) or CS, the common endogenous agonist of MR and GR (5 mg/kg s.c.) administered 1 h before stress. Intracerebroventricular infusion to intact animals 15 min before restraint of either a selective GR antagonist (A-GR, RU 38486, 100 ng/2 µl), a selective MR antagonist (A-MR, RU 28318, 100 ng/2 µl) or a combination of A-GR and A-MR (100 ng of each one/2 µl), abolished the stress-induced anxiogenic-like effect. The present findings indicate that both MR and GR are involved in the long-term CS modulation of the anxiety response induced by restraint. Both receptors mediate CS effects in an independent manner.