Biomedical subjects

I Pávó

Publications and source records attributed to I Pávó.

At least 19 recordsLinked to original sources

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

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

[Clinical experience with raloxifene].

Selective receptor modulators (SERMs) are drugs which act via the estrogen receptors and possess tissue specific estrogenic or anti-estrogenic properties. The bone and cardiovascular effects of SERMs are estrogen-like, while they have an effect as estrogen antagonist in the mammary tissues. Raloxifene is the first representative of selective estrogen receptor modulators which does not cause estrogenic effects in the uterus. Based on numerous recently completed controlled clinical trials, the authors characterize the clinical features of raloxifene to assess its therapeutic potency.

Breast Neoplasms↗

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

Synthesis of oxytocin antagonists containing conformationally constrained amino acids in position 2.

Analogues of oxytocin containing D-Trp, 2-amino-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid (Atc) or 1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (Car) with R or S configurations in position 2 were synthetized, and their receptor bindings were tested on isolated guinea-pig uterus, rat liver and rat kidney inner medulla plasma membranes. The peptides were synthetized in the solid phase by using racemates of Car and Atc. The resulting diastereomeric mixtures were separated by means of RP-HPLC. The binding to the oxytocin receptor was somewhat decreased for the Atc isomers and dramatically decreased for both R- and S-Car, while the D-Trp-containing analogue displayed a relatively high receptor affinity. However, the V1 receptor affinities were almost the same as those of the parent peptide for the Car-containing analogues and dramatically decreased for the S-Atc substituted analogue, which has a relatively high OT/V1 receptor selectivity of 44.5.

Animals↗

PubMed1999

In vivo effects of 2-substituted [Mpa1Sar7Arg8]-oxytocin antagonists on postpartum rat.

A set of oxytocin antagonists consisting of [Mpa1Sar7Arg8]-oxytocin substituted by various conformationally restricted or bulky D amino acids at position 2 were synthetized and biologically tested. In in vivo pharmacological investigations, the effects of these peptides were examined on the spontaneous motor activity of postpartum rat. Three of the newly prepared peptides proved at least as effective in inhibiting uterine contractions as clinically investigated atosiban.

Animals↗

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↗

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

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↗

PubMed1995

Effects of testosterone on the rat renal medullary vasopressin receptor concentration and the antidiuretic response.

The renal concentrating ability declines with age in humans and animals. Studies suggest that the concentrating defect is due to a decrease in renal vasopressin sensitivity. With ageing, expression of the renal vasopressin V2 receptor in rat is impaired; the normal receptor expression is restored by testosterone treatment. The effect of testosterone on the renal sensitivity to vasopressin was investigated in young rats. Male rats after orchidectomy and chronic antiandrogen cyproterone acetate treatment, and female rats after chronic testosterone phenylpropionate treatment, were used. The plasma arginine-vasopressin (AVP) and testosterone concentrations, and the antidiuretic responses to AVP and the V2 agonist deamino-[8-D-arginine]-vasopressin (dDAVP) after volume loading were measured, and the renal [3H]AVP binding density was determined. The plasma AVP level decreased slightly, but not significantly, in male rats after orchidectomy and cyproterone acetate treatment, but did not alter in female rats after testosterone treatment. The AVP and dDAVP sensitivities decreased in male rats after orchidectomy and cyproterone acetate administration, and increased in female rats treated with testosterone, as compared with the animals with a normal gonadal function. [3H]AVP binding to the renal inner medullary membranes was decreased following orchidectomy or antiandrogen treatment in male rats, and increased in testosterone-treated female rats. The results suggest that testosterone may play a physiological role in maintenance of the V2 vasopressin receptor expression and hence in the normal urinary concentrating ability in rat.

Androgen Antagonists↗

PubMed1994

Aggressive role of vasopressin in development of different gastric lesions in rats.

The effects of endogenous or exogenous vasopressin in models of gastric mucosal injury with a different pathophysiology (ethanol, indomethacin, reserpine, cold-restraint stress and haemorrhagic shock-induced lesions) were investigated in rats. [Mca1,TyrMe2,Arg8]vasopressin, a vasopressin pressor (V1) receptor antagonist, was found to reduce dose dependently the extent of the lesions in all models, and to protect the deeper layer of the mucosa (assessed by histology). Endogenous vasopressin deficiency, as in Brattleboro homozygous rats, had a similar effect. [Lys8]Vasopressin injected exogenously aggravated all types of lesions in normal rats. Circulating vasopressin levels were increased by ethanol, reserpine, cold-restraint stress and haemorrhagic shock, but not by indomethacin, whereas the intramucosal vasopressin content was found to be elevated in all models. Additionally, specific binding sites for vasopressin were shown on the blood vessels of the gastric mucosa (assessed by autoradiography). It is concluded that vasopressin plays a significant aggressive role in the generation of these types of lesions.

Animals↗

PubMed1993

Synthesis and binding characteristics of two sulfhydryl-reactive probes for vasopressin receptors.

The present study describes the synthesis and receptor binding affinities of the sulfhydryl-reactive vasopressin analogs deamino[Dab(N delta-N-maleoyl-beta-alanin e)4]AVP (1a) and deamino[Lys(N epsilon-N-maleoyl-beta-alanine)8VP (2a). The analogs were obtained by introducing the sulfhydryl-reactive maleoyl-beta-analyl group at the delta-amino group of Dab4 in deamino[Dab4]AVP (1) and at the epsilon-amino group of Lys8 in deamino[Lys8]VP (2), which were synthesized by the solid-phase method. Furthermore, the analog modified at Dab4 was prepared as tritium labeled compound (1b) after catalytic iodine tritium exchange at Tyr2 in deamino[Dab4]AVP. The sulfhydryl-reactive vasopressin analogs retained high binding affinity for the V2 vasopressin receptor in membranes derived from bovine kidney inner medulla. Apparent dissociation constants Kd of 45 nM (compound 1a) and 15 nM (compound 2a) were determined. Incubation of the ligand receptor complexes at pH 5.5 resulted in dissociation of the sulfhydryl-reactive vasopressin analogs from the V2 receptor. No indications of a covalent reaction between analogs 1a, 2a and 1b and sulfhydryl groups in or close to the hormone binding site of the V2 receptor were found.

Amino Acid Sequence↗

PubMed1993

Difference between male and female rats in vasopressor response to arginine vasopressin.

A study was carried out how the sexual difference influences the increase in blood pressure (BP) induced by arginine vasopressin (AVP), and how the binding characteristics of 3H-labelled AVP on membranes prepared from the vascular bed were affected. After the administration of various doses of AVP, a significantly higher BP increase was observed in male rats than in females. The vasopressor effect of AVP was reduced in males following orchidectomy or administration of the antiandrogen cyproterone acetate. The vasopressin (VP) antagonist d(CH2)5Tyr(Me)AVP diminished the BP response to AVP in both sexes. The plasma AVP level was found to be much higher in males than in females, but it was decreased to the level of females after orchidectomy. The density of AVP-binding sites in the aorta membrane preparation was smaller in females, and in orchidectomized or cyproterone acetate-treated male rats than in the control males. The results demonstrate that testosterone upregulates the number of AVP-binding sites, leading to an increase in the pressor response to AVP in the rat vascular bed.

Animals↗