Central moxonidine on water and NaCl intake

In this study we investigated: (a) the effects of intracerebroventricular (i.c.v.) injections of moxonidine (an alpha(2)-adrenergic and imidazoline receptor agonist) on the ingestion of water and NaCl induced by 24 h of water deprivation; (b) the effects of i.c.v. injection of moxonidine on central angiotensin II (ANG II)- and carbachol-induced water intake; (c) the effects of the pre-treatment with i.c.v, idazoxan (an alpha(2)-adrenergic and imidazoline receptor antagonist) and RX 821002 (a selective alpha(2)-adrenergic antagonist) on the antidipsogenic action of central moxonidine. Male Holtzman rats had stainless steel cannulas implanted in the lateral cerebral ventricle. Intracerebroventricular injection of moxonidine (5 and 20 nmol/1 mu l) reduced the ingestion of 1.5% NaCl solution (4.1 +/- 1.1 and 2.9 +/- 2.5 ml/2 h, respectively vs. control = 7.4 +/- 2.1 ml/2 h) and water intake (2.0 +/- 0.6 and 0.3 +/- 0.2 ml/h, respectively vs. control = 13.0 +/- 1.4 ml/h) induced by water deprivation, Intracerebroventricular moxonidine (5 nmol/1 mu l) also reduced i.c.v. ANG Ii-induced water intake (2.8 +/- 0.9 vs. control = 7.9 +/- 1.7 ml/1 h) and i.c.v. moxonidine (10 and 20 nmol/1 mu l) reduced i.c.v. carbachol-induced water intake (4.3 +/- 1.7 and 2.1 +/- 0.9, respectively vs. control = 9.2 +/- 1.0 ml/1 h). The pre-treatment with i.c.v. idazoxan (40 to 320 nmol/1 mu l) abolished the inhibitory effect of i.c.v, moxonidine on carbachol-induced water intake. Intracerebroventricular idazoxan (320 nmol/1 mu l) partially reduced the inhibitory effect of moxonidine on water deprivation-induced water intake and produced only a tendency to reduce the antidipsogenic effect of moxonidine on ANG Ii-induced water intake. RX 821002 (80 and 160 nmol/1 mu l) completely abolished the antidipsogenic action of moxonidine on ANG Ii-induced water intake. The results show that central injections c: moxonidine strongly inhibit water and NaCl ingestion. They also suggest the involvement of central alpha(2)-adrenergic receptors in the antidipsogenic action of moxonidine. (C) 1999 Elsevier B.V.

Forebrain angiotensin type 1 receptors and parabrachial serotonin in the control of NaCl and water intake

This study investigated the roles of serotonin (5-HT) receptors in the lateral parabrachial nucleus (LPBN), and brain angiotensin type 1 (AT(1)) receptors in the intake of 0.3 M NaCl and water induced by angiotensin II (ANG II). Rats were implanted with stainless steel cannulas for injections into tho subfornical organ (SFO) and into the LPBN. Bilateral LPBN pretreatment with the nonselective serotonergic 5-HT1/5-HT2 receptor antagonist methysergide (4 mu g/200 nl) markedly enhanced 0.3 M NaCl intake induced by injections of ANG II (20 ng/200 nl) into the SFO. Pretreatment of the SFO with the AT(1) receptor antagonist losartan (1 mu g/200 nl) blocked the intake of 0.3 M NaCl induced by ANG II in combination with LPBN methysergide injections. These results suggest that serotonergic mechanisms associated with the LPBN inhibit the expression of salt appetite induced by ANG II injections into Ihs SFO. In addition, the results indicate that the enhanced NaCl intake generated by central administration of ANG II in the presence of LPBN 5-HT blockade is mediated bg brain ATI receptors.

Hindbrain serotonin and the rapid induction of sodium appetite

Both systemically administered furosemide and isoproterenol produce water intake (i.e., thirst). Curiously, however, in light of the endocrine and hemodynamic effects produced by these treatments, they are remarkably ineffective in eliciting intake of hypertonic saline solutions (i.e., operationally defined as sodium appetite). Recent work indicates that bilateral injections of the serotonin receptor antagonist methysergide into the lateral parabrachial nuclei (LPBN) markedly enhance a preexisting sodium appetite. The present studies establish that a de novo sodium appetite can be induced with LPBN-methysergide treatment under experimental conditions in which only water is typically ingested. The effects of bilateral LPBN injections of methysergide were studied on the intake of water and 0.3 M NaCl following acute (beginning 1 h after treatment) diuretic (furosemide)-induced sodium and water depletion and following subcutaneous isoproterenol treatment. With vehicle injected into the LPBN, furosemide treatment and isoproterenol injection both caused water drinking but essentially no intake of hypertonic saline. In contrast, bilateral treatment of the LPBN with methysergide induced the intake of 0.3 M NaCl after subcutaneous furosemide and isoproterenol. Water intake induced by subcutaneous furosemide or isoproterenol was not changed by LPBN-methysergide injections. The results indicate that blockade of LPBN-serotonin receptors produces a marked intake of hypertonic NaCl (i.e., a de novo sodium appetite) after furosemide treatment as well as subcutaneous isoproterenol.

5-HT1A, but not 5-HT2 and 5-HT7, receptors in the nucleus raphe magnus modulate hypoxia-induced hyperpnoea

Aim: In the present study, we assessed the role of 5-hydroxytryptamine (5-HT) receptors (5-HT1A, 5-HT2 and 5-HT7) in the nucleus raphe magnus (NRM) on the ventilatory and thermoregulatory responses to hypoxia.Methods: To this end, pulmonary ventilation (V-E) and body temperature (T-b) of male Wistar rats were measured in conscious rats, before and after a 0.1 mu L microinjection of WAY-100635 (5-HT1A receptor antagonist, 3 mu g 0.1 mu L-1, 56 mM), ketanserin (5-HT2 receptor antagonist, 2 mu g 0.1 mu L-1, 36 mM) and SB269970 (5-HT7 receptor antagonist, 4 mu g 0.1 mu L-1, 103 mM) into the NRM, followed by 60 min of severe hypoxia exposure (7% O-2).Results: Intra-NMR microinjection of vehicle (control rats) or 5-HT antagonists did not affect V-E or T-b during normoxic conditions. Exposure of rats to 7% O-2 evoked a typical hypoxia-induced anapyrexia after vehicle microinjections, which was not affected by microinjection of WAY-100635, SB269970 or ketanserin. The hypoxia-induced hyperpnoea was not affected by SB269970 and ketanserin intra-NMR. However, the treatment with WAY-100635 intra-NRM attenuated the hypoxia-induced hyperpnoea.Conclusion: These data suggest that 5-HT acting on 5-HT1A receptors in the NRM increases the hypoxic ventilatory response.

Progesterone (PR), Oestrogen (ER-alpha and ER-beta) and Oxytocin (OTR) Gene Expression in the Oviduct and Uterus of Pregnant and Non-pregnant Bitches

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expression and Function of Fibroblast Growth Factor 18 in the Ovarian Follicle in Cattle

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Contribution of the rostral ventromedial medulla to post-anxiety induced hyperalgesia

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Ionotropic Glutamate Receptors in Hypothalamic Paraventricular and Supraoptic Nuclei Mediate Vasopressin and Oxytocin Release in Unanesthetized Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Agents that inhibit histamine release: A review

It is well known that histamine is found in high concentration in mast cell granules(1). The histamine content of these granules may be released to the extracellular space if an appropriate stimulus is provided(2). Besides histamine, other preformed active substances like enzymes, chemotatic factors and proteoglycans, as well as newly generated mediators like eicosanoids, platelet activating factor and adenosine are released during the secretion process of mast cells(3). The activation of mast cell degranulation has been associated with a number of pathologic disorders, most frequently, diseases derived from the atopic state(4). It is now evident that mast cells are the primary effector cells in the early reaction in both allergic and non-allergic asthma(5,6), although some authors doubt that the late reaction of asthma is a mast cell dependent event(6). Other studies point towards basophils as cellular elements involved in the secondary phase of inflammation in allergic diseases(7). Secretion would depend on a histamine releasing factor, and on the presence of IgE on the basophil's surface(8). There is also evidence suggesting involvement of mast cells in some non-allergic inflammatory processes like arthritis(9). The pharmacological management of these diseases basically consists in the use of methylxantines, beta 2-adrenergic agonists, glucocorticoids, sodium cromoglycate-like drugs, anticholinergic and antihistaminic H 1 antagonists(10). Their therapeutic effects include bronchodilatation, receptor and physiological antagonism, prevention of inflammatory responses induced by secondary cells, and finally, inhibition of mast cell activation(11). This review is concerned with compounds having inhibitory action on mast cell activation, and their possible importance on the pathophysiology of mast cell-related diseases.

Different effects on rat arterial pressure and heart rate when losartan is injected into the third or fourth ventricle

Cardiovascular responses to central losartan (LOS), a non-peptide angiotensin II (ANG II) receptor antagonist, were investigated by comparing the effects of LOS injection into the 3rd and 4th cerebral ventricles (3rdV, 4thV) on mean arterial pressure (MAP) and heart rate (HR). Adult male Holtzman rats were used (N=6 animals per group). Average basal MAP and HR were 114±3 mmHg and 343±9 bpm (N=23), respectively. LOS (50, 100 or 200 nmol/2 μl) injected into the 3rdV induced pressor (peak of 25±3 mmHg) and tachycardic (peak of 60±25 bpm) responses. LOS injected into the 4thV had no effect on MAP, but it induced bradycardia (peak of -35±15 bpm). KCl (200 nmol/2 μl) injected into the 3rdV or into the 4thV had no effect on either MAP or HR compared to 0.9% saline injection. The results indicate that LOS injected into the third ventricle acts on forebrain structures to induce its pressor and tachycardic effects and that bradycardia, likely dependent on hindbrain structures, is obtained when LOS is injected into the fourth ventricle.

Effects of intracerebroventricular injections of losartan or PD123319 on arterial pressure and heart rate of sodium replete and sodium deplete rats

Angiotensin II (Ang II) non-peptide antagonists were injected i.c.v. (6.25-200 nmol, n = 5-8 rats/group): In sodium replete rats, losartan (AT1 receptor antagonist) induced an increase in mean arterial pressure (MAP) and in heart rate (HR) by 3rd ventricular (3rdV) injection, and a weaker pressor response and bradycardia by 4th ventricular (4thV) injection. PD123319 (AT2 receptor antagonist) induced an increase in MAP and in HR by 3rdV injection, and an increase in MAP and no alteration in HR by 4thV injection. In sodium deplete (furosemide plus removal of ambient sodium for 24 h) rats, losartan induced an increase in MAP and no alteration in HR by 3rdV injection, and no alteration in MAP and bradycardia by 4thV injection. PD123319 induced an increase in MAP and in HR by 3rdV injection, and an increase in MAP and bradycardia by 4thV injection. Thus, there was no fall in MAP by central injections of Ang II antagonists. Intravenous injection of losartan, but not of PD123319, induced a fall in MAP in both sodium replete and sodium deplete animals. Therefore, losartan and PD123319 can have similar effects on MAP and HR when injected intracerebroventricularly, although some differences are also present. The bradycardia is consistent with an withdrawal of Ang II inhibitory action on baroreflex.

On a dual role for clonidine stimulation of the ventromedial nucleus of the hypothalamus in sodium and potassium renal excretions of rats

The effects of clonidine on sodium and potassium excretions were examined after previous administration of prazosin (an α 1-adrenergic receptor antagonist) and yohimbine (an α 2-adrenergic receptor antagonist) into the ventromedial nucleus of the hypothalamus of conscious rats. Clonidine injected into the ventromedial nucleus of the hypothalamus induced inhibitory and facilitatory effects on the urinary sodium and potassium excretions. The results suggest that facilitatory effects of clonidine on natriuresis and kaliuresis are mediated through activation of α 1-adrenoceptors and that inhibitory effects require α(2A)-adrenoceptors.

Juvenile localized scleroderma: Clinical and epidemiological features in 750 children. An international study

Objective. Juvenile localized scleroderma (JLS) includes a number of conditions often grouped together. With the long-term goal of developing uniform classification criteria, we studied the epidemiological, clinical and immunological features of children with JLS followed by paediatric rheumatology and dermatology centres. Methods. A large, multicentre, multinational study was conducted by collecting information on the demographics, family history, triggering environmental factors, clinical and laboratory features, and treatment of patients with JLS. Results. Seven hundred and fifty patients with JLS from 70 centres were enrolled into the study. The disease duration at diagnosis was 18 months. Linear scleroderma (LS) was the most frequent subtype (65%), followed by plaque morphea (PM) (26%), generalized morphea (GM) (7%) and deep morphea (DM) (2%). As many as 15% of patients had a mixed subtype. Ninety-one patients (12%) had a positive family history for rheumatic or autoimmune diseases; 100 (13.3%) reported environmental events as possible trigger. ANA was positive in 42.3% of the patients, with a higher prevalence in the LS-DM subtype than in the PM-GM subtype. Scl70 was detected in the sera of 3% of the patients, anticentromere antibody in 2%, anti-double-stranded DNA in 4%, anti-cardiolipin antibody in 13% and rheumatoid factor in 16%. Methotrexate was the drug most frequently used, especially during the last 5 yr. Conclusion. This study represents the largest collection of patients with JLS ever reported. The insidious onset of the disease, the delay in diagnosis, the recognition of mixed subtype and the better definition of the other subtypes should influence our efforts in educating trainees and practitioners and help in developing a comprehensive classification system for this syndrome. © 2006 Oxford University Press.

Endothelial and neuronal nitric oxide synthase inhibitors influences angiotensin II pressor effect in central nervous system

The present study investigated the central role of angiotensin II and nitric oxide on arterial blood pressure (MAP) in rats. Losartan and PD123349 AT 1 and AT 2 (selective no peptides antagonists angiotensin receptors), as well as FK 409 (a nitric oxide donor), N W-nitro-L-arginine methyl ester (L-NAME) a constituve nitric oxide synthase inhibitor endothelial (eNOSI) and 7-nitroindazol (7NI) a specific neuronal nitric oxide synthase inhibitor (nNOSI) were used. Holtzman strain, (Rattus norvergicus) weighting 200-250 g were anesthetized with zoletil 50 mg kg -1 (tiletamine chloridrate 125 mg and zolazepan chloridrate 125 mg) into quadriceps muscle anda stainless steel cannula was stereotaxically implanted into their Lateral Ventricle (LV). Controls were injected with a 0.5 μl volume of 0.15 M NaCl. Angiotensin II injected into LV increased MAP (19±3 vs. control 3±1 mm Hg), which is potentiated by prior injection of L-NAME in the same site 26±2 mm Hg. 7NI injected prior to ANG II into LV also potentiated the pressor effect of ANG II but with a higher intensity than L-NAME 32±3 mm Hg. FK 409 inhibited the pressor effect of ANG II (6±1 mm Hg). Losartan injected into LV before ANG II influences the pressor effect of ANG II (8±1 mm Hg). The PD 123319 decreased the pressor effects of ANG II (16±1 mm Hg). Losartan injected simultaneously with FK 409 blocked the pressor effect of ANG II (3±1 mm Hg). L-NAME produced an increase in the pressor effect of ANG II, may be due to local vasoconstriction and all at once by neuronal NOS inhibition but the main effect is of the 7-NIT an specific nNOS inhibitor. The AT 1 antagonist receptors improve basal nitric oxide (NO) production and release. These data suggest the involvement of constitutive and neuronal NOS in the control of arterial blood pressure induced by ANG II centrally, evolving AT 1 receptor-mediated vasoconstriction and AT 2 receptor-mediated vasodilatation. These results were confirmed by the experiment using FK 409. © 2006 Asian Network for Scientific Information.

Nitrergic pathways and L-type calcium channel of MnPO influencing cardiovascular homeostasis

The median preoptic nucleus (MnPO) is one of most important site of the lamina terminalis implicated in the regulation of hydro electrolytic and cardiovascular balance. The purpose of this study was to determine the effect of L-Type calcium channel antagonist, nifedipine, on the increase of median arterial blood pressure (MAP) induce by angiotensin II (ANG II) injected into the MnPO. The influence of nitric oxide (NO) on nifedipine antipressor action has also been studied by utilizing N W-nitro-L-arginine methyl ester (L-NAME) (40 μg 0.2 μL -1) a NO synthase inhibitor (NOSI), 7-nitroindazole (7-NIT) (40 μg 0.2 μL -1), a specific neuronal NO synthase inhibitor (nNOSI) and sodium nitroprusside (SNP) (20 μg 0.2 μL -1) a NO donor agent. We have also investigated the central role of losartan and PD123349 (20 nmol 0.2 μL -1), AT 1 and AT 2, respectively (selective non peptide ANG II receptor antagonists), in the pressor effect of ANG II (25 pmol 0.2 μL -1) injected into the MnPO. Male Wistar rats weighting 200-250 g, with cannulae implanted into the MnPO were utilized. Losartan injected into the MnPO, prior to ANG II, blocked the pressor effect of ANGII. PD 123319 only decreased the pressor effect of ANG II. Rats pre-treated with either 50 μg 0.2 μL -1 or 100 μg 0.2 μL -1 of nifedipine, followed by 25 pmol 0.2 μL -1 of ANG II, decreased ANG II-pressor effect. L-NAME potentiated the pressor effect of ANG II. 7-NIT injected prior to ANG II into the MnPO also potentiated the pressor effect of ANGII but with less intensity than that of L-NAME. SNP injected prior to ANG II blocked the pressor effect of ANG II. The potentiation action of L-NAME and 7-NIT on ANG II-pressor effect was blocked by prior injection of nifedipine. The results described in this study provide evidence that calcium channels play important roles in central ANG II-induced pressor effect. The structures containing NO in the brain, such as MnPO, include both endothelial and neuronal cells, which might be responsible for the influence of nifedipine on the pressor effect of ANG II. These data have shown the functional relationship between L-Type calcium channel and a free radical gas NO in the MnPO, on the control of ANG II-induced pressor effect acting in AT 1 and AT 2 receptors.