Biomedical subjects

F László

Publications and source records attributed to F László.

At least 19 recordsLinked to original sources

PubMed2006

Histamine-induced enhancement of vasopressin and oxytocin secretion in rat neurohypophyseal tissue cultures.

The effects of histamine (HA) on vasopressin (VP) and oxytocin (OT) secretion were studied in 13-14-day cultures of isolated rat neurohypophyseal (NH) tissue. The VP and OT contents of the supernatant were determined by radioimmunoassay (RIA) after a 1 or 2-h incubation. Significantly increased levels of VP and OT production were detected in the tissue culture media following HA administration, depending on the HA dose. The elevation of NH hormone secretion could be partially blocked by previous administration of the HA antagonist mepyramine (MEP, an H1 receptor antagonist) or cimetidine (CIM, an H2 receptor antagonist). Thioperamide (TPE, an H3-H4 receptor antagonist) did not influence the VP or OT secretion increase induced by HA. The application of MEP, CIM or TPE after HA administration proved ineffective. The H1 and H2 receptors are mainly involved in the HA-induced increase of both VP and OT secretion in isolated NH tissue cultures. The results indicate that NH hormone release is influenced directly by the histaminergic system, and the histaminergic control of VP and OT secretion from the NH tissue in rats can occur at the level of the posterior pituitary.

Animals↗

PubMed2005

Serotonin-induced enhancement of vasopressin and oxytocin secretion in rat neurohypophyseal tissue culture.

The effects of serotonin (5-hydroxytryptamine; 5-HT) on vasopressin (VP) and oxytocin (OT) secretion were studied in 13-14-day cultures of isolated rat neurohypophyseal (NH) tissue. The VP and OT contents of the supernatant were determined by radioimmunoassay after a 1 or 2 h incubation. Significantly increased levels of VP and OT production were detected in the tissue culture media following 5-HT administration, depending on the 5-HT dose. The elevation of NH hormone secretion could be partially blocked by previous administration of the 5-HT antagonist ketanserin or metergoline. WAY-100635 did not influence the increased VP secretion induced by 5-HT, but the elevated OT production was prevented by WAY-100635 before 5-HT administration. The application of WAY-100635, ketanserin or metergoline, after 5-HT administration proved ineffective. The results indicate that NH hormone release is influenced directly by the serotonergic system. The serotonergic control of VP and OT secretion from the NH tissue in rats can occur at the level of the posterior pituitary.

Animals↗

PubMed2003

Inhibitory effect of galanin on dopamine induced increased oxytocin secretion in rat neurohypophyseal tissue cultures.

The regulation of oxytocin (OT) release by galanin (GAL) at the neurohypophyseal (NH) nerve terminal is not adequately understood. The effect of GAL on the secretion of OT was studied in 13- to 14-day cultures of isolated rat NH tissue. By this time, the hormone content of the medium had become constant. The OT content of the supernatant medium was determined by RIA after a 1- or 2-h incubation. A significantly decreased content of OT was found following incubation with 10(-6)-10(-8) M doses of GAL. Dopamine (DA) and the DA-active drugs apomorphine (APM) and Pro-Lys-Gly (PLG) (10(-6) M in each medium) increased the OT synthesis of NH tissue cultures. This elevation of OT secretion could be blocked by the administration of GAL together with DA, APM or PLG. The DA-blocking effect of GAL was prevented by previous treatment with the GAL receptor antagonist galantid (M15). The results indicate that OT release from the NH is directly influenced by the GAL-ergic system. The GAL-ergic control of OT secretion from NH tissue in rats can occur at the level of the posterior pituitary.

Animals↗

PubMed2002

Inhibitory effect of galanin on dopamine-induced enhanced vasopressin secretion in rat neurohypophyseal tissue cultures.

The effect of galanin (GAL) on vasopressin (VP) secretion was studied in 13-14-day cultures of isolated rat neurohypophyseal (NH) tissue. The VP content of the supernatant was determined by radioimmunoassay (RIA) after a 1- or 2-h incubation. A significantly decreased content of VP was detected following the administration of 10(-6)-10(-9) M doses of GAL. Dopamine (DA) and the DA-active drugs apomorphine (APM) and Pro-Lys-Gly (PLG) (10(-6) M in each medium) increased the VP level of NH tissue cultures. This VP concentration elevation could be blocked by the administration of GAL together with DA, APM or PLG. The DA-blocking effect of GAL was prevented by previous treatment with the GAL receptor antagonist galantid (M15). The results indicate that VP release is directly influenced by the GAL-ergic system. The GAL-ergic control of VP secretion from NH tissue in rats can occur independently of the hypothalamus, at the level of the posterior pituitary.

Animals↗

PubMed2001

Helicobacter pylori lipopolysaccharide-provoked injury to rat gastroduodenal microvasculature involves inducible nitric oxide synthase.

The actions of a purified Helicobacter pylori lipopolysaccharide (3 mg x kg(-1), i.v.) on rat gastric antral and duodenal microvascular integrity (determined as radiolabelled albumin leakage) and the expression of the inducible nitric oxide (NO) synthase (iNOS; assessed by the citrulline assay) were investigated 4 h after challenge. Significant increases of albumin leakage and expression of iNOS in both antral and duodenal tissues were observed following challenge. Concurrent administration of the selective iNOS inhibitor, 1400W (N-(8-(aminomethyl)benzyl)-acetamidine; 0.2-1 mg x kg(-1), s.c.), with lipopolysaccharide, caused a dose-dependent attenuation of the gastric and duodenal albumin leakage. Thus, H. pylori lipopolysaccharide can initiate the expression of iNOS in the stomach and duodenum following systemic challenge, which can provoke gastroduodenal microvascular dysfunction.

Amidines↗

PubMed2001

Vasopressin pressor receptor-mediated activation of HPA axis by acute ethanol stress in rats.

The plasma arginine vasopressin (AVP), ACTH, and corticosterone levels and the hypothalamic corticotropin-releasing hormone (CRH) content were measured after oral administration of 1 ml of 75% ethanol to rats, a model known to induce acute gastric erosions and stress. Elevated plasma AVP, ACTH, and corticosterone levels were detected 1 h after ethanol administration. Treatment with the vasopressin pressor (V(1)) receptor antagonist [d(CH(2))(5)Tyr(Me)-AVP] before ethanol administration significantly reduced the ACTH and corticosterone level increases. A higher hypothalamic CRH content was measured at 30 or 60 min after ethanol administration. V(1) receptor antagonist injection, 5 min before ethanol administration, inhibited the rise in hypothalamic CRH content. The protein synthesis blocker cycloheximide prevented the hypothalamic CRH content elevation after stress. The AVP-, CRH-, and AVP + CRH-induced in vitro ACTH release in normal anterior pituitary tissue cultures was also prevented by pretreatment with the V(1) receptor antagonist. The results support the hypothesis that stress-induced AVP may not only act directly on the ACTH producing anterior pituitary cells but also indirectly at the hypothalamic level via the synthesis and release of CRH.

Adrenocorticotropic Hormone↗

PubMed2000

Raloxifene, an oestrogen-receptor modulator, prevents decreased constitutive nitric oxide and vasoconstriction in ovariectomized rats.

Administration of graded doses of [Arg(8)]vasopressin (0.06-0.18 microg kg(-1), i.v.) induced a dose-dependent increase in arterial blood pressure in the catecholamine-depleted (phentolamine; 10 mg kg(-1), i.p.) intact and ovariectomized female rat, with the elevation of blood pressure more marked following ovariectomy. In addition, ovariectomy caused the down-regulation of aortic Ca(2+)-dependent constitutive nitric oxide synthase (assessed by the citrulline assay). The down-regulation of the Ca(2+)-dependent constitutive nitric oxide synthase and augmentation of vasopressin-induced blood pressure responses were prevented by the therapy (1 month, p.o.) with the selective oestrogen receptor modulator, raloxifene (0.3-1.0 mg kg(-1) day(-1)), or with 17beta-oestradiol (0.3 mg kg(-1) day(-1)) in ovariectomized rats. Thus, oestrogen deficiency down-regulates vascular constitutive nitric oxide synthase, which appears to be involved in the increased sensitivity of the vasculature to vasopressin, since both effects can be reversed by the exogenous administration of the natural oestrogen 17beta-oestradiol or the selective oestrogen-receptor modulator raloxifene.

Animals↗

PubMed2000

Estrogen-mediated up-regulation of the Ca-dependent constitutive nitric oxide synthase in the rat aorta and heart.

The role of endogenous estrogens has been studied in the regulation of the Ca-dependent constitutive nitric oxide synthase (cNOS) enzyme activity in aortic and cardiac tissues of the rat. The activity of cNOS enzyme was measured by the citrulline assay in the abdominal aorta and in the left ventricle of the heart obtained from male, sham-operated female and ovariectomized female Wistar rats. Estrogen replacement therapy (17-beta-estradiol, 20-100 microg/kg/day, s.c.) has been performed in ovariectomized rats over two weeks. We found that cNOS activity was higher in the aorta and heart of female rats compared to males. Ovariectomy decreased cNOS activity in both tissues to that level what could be observed in males. Estrogen supplementation caused a dose-dependent elevation of cNOS enzyme activity in cardiac and aortic tissues, where the higher dose (100 microg) completely restored cNOS enzyme activity to the levels found in females. We concluded that endogenous estrogens up-regulate the activity of the cNOS isoenzymes in the rat aorta and heart.

Animals↗

PubMed2000

Interactions of pro-inflammatory and vasoactive mediators with nitric oxide in the regulation of rat vascular permeability during laparotomy.

Inhibition of constitutive nitric oxide (NO) synthases by administration of N(G)-nitro-L-arginine methyl ester (L-NAME) during abdominal laparotomy provokes extensive vascular leakage in the rat gastrointestinal tract, assessed by the extravasation of [125I]human serum albumin. In the present study, the role of vasoactive or neutrophil-derived pro-inflammatory mediators in this process has been investigated. Administration of the thromboxane synthase inhibitor, 1-benzyl-imidazole (BZI, 25-50 mg kg(-1), s.c.), the platelet-activating factor (PAF) receptor antagonist, 3-[4-(2-chlorophenyl)-9-methyl-6H-thienol-[3,2-f][1,2,4]-triazolo- [4, 3-a][1,4]-diazepine-2-yl]-1-(4-morpholynil)-1-propionate (WEB 2086; 0.5-1 mg kg(-1), s.c.), the 5-lipoxygenase synthase inhibitor, N-(4-benzyloxybenzyl)-acetohydroxamic acid (BW A137C; 4-20 mg kg(-1), s.c.) or the vasopressin pressor receptor antagonist ([Mca(1), Tyr(Me)(2),Arg(8)]vasopressin/Manning peptide; 0.01-0.2 microg kg(-1), s.c.) dose-dependently reduced the intestinal plasma leakage provoked by L-NAME (5 mg kg(-1), s.c.), following a 5-cm abdominal laparotomy in anaesthetised rats. These findings suggest that constitutive NO synthase effectively counteracts the damaging actions on microvascular integrity of mediators, including thromboxanes, PAF, leukotrienes and vasopressin, released during surgical intervention.

Albumins↗

PubMed2000

Nitric oxide-mediated mucus hypersecretion protects the stomach of ovariectomized rats.

The actions of ovariectomy on nitric oxide synthase (assessed by the citrullin assay), mucus secretion (assessed by the Alcyan blue technique) and ulcerogenic response (indomethacin (30 mg kg(-1), s.c. , 4 h) or cysteamine (400 mg kg(-1), s.c., 24 h)) were studied in the female rat stomach. Ovariectomy increased nitric oxide synthase and mucus secretion, and decreased the severity of lesions, effects reversed by the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 10 mg kg(-1), s.c., 4 h before measurements). Therefore, estrogen-deficiency protects the gastric mucosa by nitric oxide (NO)-mediated mucus hypersecretion.

Animals↗

PubMed2000

Site-specific lesion formation, inflammation and inducible nitric oxide synthase expression by indomethacin in the rat intestine.

The involvement of nitric oxide (NO) formed by the inducible isoform of NO synthase (iNOS) has been investigated in the development of rat intestinal lesions following indomethacin administration. Over a 72-h period, indomethacin (10 mg kg(-1), s.c.) provoked a time-dependent increase in expression of iNOS (assessed by the conversion of radiolabelled L-arginine to citrulline) and enhancement of vascular leakage of radiolabelled human serum albumin in the jejunum which commenced 18 h after indomethacin. Similar effects were not observed in the ileum, colon or caecum. In addition, macroscopic lesions were detectable and myeloperoxidase activity (an index of neutrophil recruitment) were increased in the rat jejunum 18-24 h after indomethacin, but remained at basal levels in the ileum and colon. These findings suggest that indomethacin provokes a site-selective expression of iNOS in the rat jejunum which correlates with lesion formation and vascular leakage, whereas both the ileum and colon are spared.

Animals↗

PubMed1999

Nitric oxide modulates the gastrointestinal plasma extravasation following intraabdominal surgical manipulation in rats.

The actions of nitric oxide (NO) on gastrointestinal plasma loss, assessed by the leakage of [125I]human serum albumin, provoked by intraabdominal surgery and organ manipulation has been investigated in pentobarbitone-anaesthesized rats. Gentle manipulation (3 min) of the stomach or the small intestine following laparotomy leads to an increase in albumin extravasation in the stomach, duodenum, jejunum and colon over 1 h. Administration of the NO synthase inhibitors, N(G)-nitro-L-arginine methyl ester (1-5 mg kg(-1), s.c.) and N(G)-monomethyl-L-arginine (12.5-50 mg kg(-1), s.c.), provoked a further substantial elevation of gastrointestinal albumin extravasation in the surgically manipulated rat, but not in control rats. This effect could be prevented by the pretreatment (15 min) with L-arginine (300 mg kg(-1), s.c.) or by the concurrent infusion of the NO donor, S-nitroso-glutathione (5 microg kg(-1) min(-1), i.v.). Endogenous NO, most likely formed by endothelial NO synthase, thus appears to maintain microvascular integrity during surgery and organ manipulation of the gastrointestinal tract.

Anesthesia↗

PubMed1999

Detrimental effects of oestradiol on cysteamine-induced gastroduodenal ulceration in the female rat.

The actions of the female sex steroid, oestradiol on cysteamine-induced mucosal ulceration has been evaluated in female Wistar rats. Administration of cysteamine (400 mg x kg(-1), s.c.) provoked macroscopic gastroduodenal mucosal injury (assessed planimetrically) and an increase in microvascular permeability (assessed by the extravasation of radiolabeled albumin) in the stomach and duodenum, determined 24 h later. Ovariectomy (2 weeks before cysteamine) reduced gastroduodenal macroscopic injury, and albumin extravasation following cysteamine challenge. Administration of oestradiol (1-5 mg x kg(-1), as an i.m. depot 1 week before cysteamine) dose-dependently augmented gastric and duodenal macroscopic mucosal lesions and microvascular permeability provoked by cysteamine. These findings indicate that oestradiol can exacerbate gastroduodenal ulceration and microvascular injury.

Animals↗

PubMed1999

Endogenous nitric oxide in the maintenance of rat microvascular integrity against widespread plasma leakage following abdominal laparotomy.

1. The role of nitric oxide (NO) in the maintenance of microvascular integrity during minor surgical manipulation has been evaluated in the rat. 2. The NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME, 5 mg kg(-1), s.c.) and N(G)-monomethyl-L-arginine (L-NMMA, 50 mg kg(-1), s.c.) had no effect on microvascular leakage of radiolabelled albumin over 1 h in the stomach, duodenum, jejunum, colon, lung and kidney in the un-operated conscious or pentobarbitone-anaesthetized rat. 3. In contrast, in anaesthetized rats with a midline abdominal laparotomy (5 cm), L-NAME (1-5 mg kg(-1), s.c.) or L-NMMA (12.5-50 mg kg(-1), s.c.) dose-dependently increased gastrointestinal, renal and pulmonary vascular leakage, effects reversed by L-arginine pretreatment (300 mg kg(-1), s.c., 15 min). These actions were not observed in anaesthetized rats that had only received a midline abdominal skin incision (5 cm). 4. Pretreatment with a rabbit anti-rat neutrophil serum (0.4 ml kg(-1), i.p.), 4 h before laparotomy, abolished the plasma leakage induced by L-NAME in all the organs investigated. 5. These results indicate that the following abdominal laparotomy, inhibition of constitutive NO synthase provokes vascular leakage in the general microcirculation, by a process that may involve neutrophils. Such effects could thus confound studies on the microvascular actions of NO synthase inhibitors using acute surgically prepared in vivo models. The findings thus suggest that constitutively-formed NO has a crucial role in the maintenance of acute microvascular integrity following abdominal surgical intervention.

Abdomen↗

PubMed1998

Endogenous vasopressin increases acute endotoxin shock-provoked gastrointestinal mucosal injury in the rat.

Administration of a low dose of endotoxin (from Escherichia coli, 3 mg kg(-1), i.v.), which does not affect vascular permeability or blood pressure over 1 h, leads to the release of endogenous vasopressin and damage to the mucosal microvasculature. Thus, endogenous vasopressin could be involved in septic shock. In the present study, we investigated the role of endogenous vasopressin in gastrointestinal mucosal injury induced by acute endotoxin shock, which was generated in rats by administering a high dose of E. coli endotoxin (50 mg kg(-1), i.v.). Tissues were removed 15 min after endotoxin. The vasopressin V1 receptor antagonist, d[CH2]5Tyr[Me]arginine-vasopressin (0.2-1 microg kg(-1), i.v.), was injected 10 min before endotoxin. Monastral blue (30 mg kg(-1), i.v.), which stains damaged vasculature, was injected 10 min before autopsy. Endotoxin reduced systemic arterial blood pressure (from 115+/-5 to 42+/-4 mmHg), generated macroscopic and microvascular injury, and elevated plasma vasopressin levels (from 3.4+/-0.2 to 178+/-16 pg ml(-1)). The vasopressin V1 receptor antagonist reduced this macroscopic injury, and in the vasopressin-deficient Brattleboro rat a similar reduction of gastrointestinal mucosal damage was found. Substantial decreases in endotoxin-induced microvascular damage were observed in each tissue, e.g., the gastric Monastral blue staining was reduced by 47+/-3% and 96+/-3% (P < 0.01) after vasopressin V1 receptor antagonist treatment and in Brattleboro rats, respectively. Vasopressin, acting through its V1 receptors, thus appears to be involved in acute endotoxin shock-provoked gastrointestinal injury.

Animals↗

PubMed1998

Role of nitric oxide and platelet-activating factor in the initiation of indomethacin-provoked intestinal inflammation in rats.

The effect of indomethacin following the concurrent administration of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on acute intestinal microvascular permeability has been investigated in the rat. Administration of indomethacin (10 mg/kg, s.c.) or L-NAME (10 mg/kg, s.c.) alone did not affect jejunal and ileal vascular permeability over a 12 h period, as determined by the leakage of radiolabelled serum albumin. By contrast, when indomethacin (10 mg/kg, s.c.) was injected concurrently with L-NAME (2-10 mg/kg, s.c.) significant time-dependent plasma leakage occurred in intestinal tissues over 12 h, being apparent within 1 h. Pretreatment with L-arginine (300 mg/kg, s.c.) 15 min prior L-NAME prevented these changes in microvascular permeability. Likewise, pretreatment with the platelet-activating factor receptor antagonist, WEB 2086 ((3-[4-(2-chlorophenyl)-9-methyl-6H-thienol[3,2-f][1,2,4]triazolo- [4,3-a][1,4]diazepine-2-yl]-1-(4-morpholynil)-1-propanone), 0.1-1 mg/kg, s.c.) dose-dependently attenuated such damage. These findings suggest that following indomethacin administration, the early inhibition of NO synthase leads to acute microvascular injury involving platelet-activating factor in the rat jejunum and ileum, indicating a protective role of NO, formed by constitutive NO synthase.

Animals↗

PubMed1998

Deleterious action of vasopressin in gastroduodenal ulceration: experimental and clinical observations.

Vasopressin, released from the posterior pituitary and from the vascular endothelium, can cause vasoconstriction and provoke platelet aggregation, leading to an impaired tissue blood supply. In humans with pituitary diabetes insipidus the central release of vasopressin is diminished, and in the Brattleboro homozygous rat there is congenitally no synthesis of this hormone. The gastroduodenal intramucosal vasopressin level is elevated in normal rats following various acute ulcerogenic challenges (after ethanol, reserpine, indomethacin, cold-restraint stress, endotoxin shock and hemorrhagic shock), and vasopressin-deficient rats are less sensitive to these stimuli. In a hospital- and population-based case-control, age-matched retrospective study, the incidence of human gastroduodenal ulceration is significantly higher in the normal population (in whom the release of vasopressin is presumed to be intact) than in the vasopressin-deficient one (central diabetes insipidus patients). In conclusion, endogenous vasopressin plays an aggressive role in development of gastroduodenal ulceration, especially that related to stress.

Adult↗

PubMed1997

Damaging actions of testosterone on cysteamine-induced gastroduodenal ulceration and vascular leakage in the rat.

The sexual dimorphism of gastroduodenal ulceration is suggested on the basis of clinical and experimental observations. This difference probably relates to the actions of endogenous sexual steroids. In the present study, the role of testosterone was evaluated in the generation of gastroduodenal mucosal injury provoked by cysteamine (400 mg/kg, s.c.). We found that macroscopic mucosal damage and microvascular (125)I-human serum albumin leakage (2 microCi/kg, i.v.) developed in the stomach and duodenum of male rats 24 h after the administration of cysteamine. This mucosal injury was prevented by orchidectomy and by the pretreatment with the antiandrogen, cyproterone acetate (12 mg/kg per day for 8 consecutive days). It was also shown that pretreatment with testosterone (4-20 mg/kg per week) dose-dependently aggravated cysteamine-induced gastroduodenal mucosal injury. Our results thus suggest an aggressive role of testosterone in the generation of cysteamine-induced gastroduodenal ulceration.

Androgen Antagonists↗