Lateral parabrachial nucleus and central amygdala in the control of sodium intake

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

Severe food restriction induces myocardial dysfunction related to SERCA2 activity

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

The importance of androgen on noradrenergic responses of vas deferens isolated from acutely stressed rats

This study investigated the importance of androgen on responses to alpha and beta (norepinephrine) and alpha(1) (phenylephrine and methoxamine) agonists in vasa deferentia isolated from adult, immature, cryptorchid, and castrated rats submitted to swimming-induced acute stress. The participation of adrenergic nervous terminals was also investigated. Acute stress was shown to induce a significant subsensitivity to norepinephrine only in vas deferens from adult rats with normal levels of androgens. In addition, sympathetic denervation of the vas deferens prevented the appearance of subsensitivity. Subsensitivity was not seen when the experiments were carried out using phenylephrine and methoxamine. This shows that subsensitivity to norepinephrine in this acute stress situation may depend on other factors such as neuronal uptake, but not on alpha(1)-adrenoceptor response. Thus, when animals are exposed to acute stressogenic situations, this subsensitivity requires physiological levels of androgens to establish, and may also be involved in body homeostasis. (C) 1999 Academic Press.

The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha(1B)-adrenoceptors

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

INJECTION OF RAMIPRIL INTO THE LATERAL VENTRICLE INTERFERES WITH THE DRINKING RESPONSE INDUCED BY PHARMACOLOGICAL AND NATURAL THIRST STIMULI

We investigated the effects of ramipril, an angiotensin I-converting enzyme (ACE) inhibitor, on water intake by male Holtzman rats (250-300 g) with cannulae implanted into the lateral ventricle. Intracerebroventricular (icv) injection of ramipril (1 mu g/mu l) significantly reduced drinking in response to subcutaneous (sc) injection of isoprenaline (100 mu g/kg) from 8.49 +/- 0.69 to 2.96 +/- 0.36 ml/2 h, polyethyleneglycol (PEG) (30% w/v, 10 ml/kg) from 9.51 +/- 2.20 to 1.6 +/- 0.34 ml/2 h or water deprivation for 24 h from 12.61 +/- 0.83 to 5.10 +/- 1.37 ml/2 h. Ramipril had no effect on water intake induced by cellular dehydration produced by sc injection of hypertonic saline (2 M NaCl). These results are consistent with the hypothesis that ramipril acts as an ACE-blocking agent in the brain. The possibility that ramipril is transformed to ramiprilat, the active drug, by the brain is suggested.

THE USE OF AMPPD AS AN ALTERNATIVE SUBSTRATE FOR AP-MEDIATED DETECTION OF NONRADIOLABELED DNA PROBES IN EUCALYPTUS-SALIGNA

We present a non-radioactive alternative to Southern's (J. Mol. Biol. 98: 503-517, 1975) DNA-DNA hybridization technique. The use of AMPPD - Disodium 3-(4-Methoxyspiro {1,2-dioxetane-3,2'tricyclo[3.3.1.1(3,7)]decan}-4-yl)phyenyl phosphate as an alternative substrate for AP-mediated detection of digoxigenin-11 dUTP-labeled probes made possible the simple and nonhazardous reuse of blots. We used 0.8 % agarose gels containing 30 mug per lane of Eucalyptus saligna DNA, digested with Eco RI, electrophoresed and blotted on to nylon membranes (Hybond-N, Amersham, UK), using the Southern blotting procedure, and UV irradiated for one minute for DNA fixation. The hybridizations were carried out overnight with digoxigenin labeled random inserts of E. saligna DNA by using the Genius Kit (Boehringer Mannheim). Detection of the DNA-DNA hybrids was performed in the presence of 0.5% blocking agent and the substrates NBT/BCIP were replaced by 0.26 mM AMPPD in the final alkaline assay buffer (50 mul/cm2). After membrane incubation for five minutes at room temperature in a sealed plastic bag, the AMPPD solution was retrieved and stored at 4-degrees-C for reuse. A Kodak X-BRAF QA-S film was pressed firmly onto the bag containing the wet membrane, exposed for two to six hours and then developed. After use, the probes were stripped off and the blots reutilized, three times so far, with the same results.

Idazoxan and the effect of intracerebroventricular oxytocin or vasopressin on sodium intake of sodium-depleted rats

The alpha(2)-adrenergic agonist clonidine and the neuropeptide oxytocin, inhibit sodium intake when injected intracerebroventricularly (i.c.v.). The present work investigates whether (1) vasopressin also inhibits sodium intake when injected i.c.v., and (2) the effect of oxytocin and of vasopressin on sodium intake is affected by i.c.v. injection of idazoxan, an alpha(2)-adrenergic antagonist. Clonidine (30 nmol), oxytocin (40, 80 nmol) and vasopressin (40, 80 nmol) were injected i.c.v. 20 min prior to a 1.5% NaCl appetite test, in rats depleted of sodium for 24 h by a combination of a single s.c. injection of furosemide (10 mg/rat) and removal of ambient sodium. Every dose of clonidine, oxytocin and vasopressin inhibited the 1.5% NaCl intake. Seizures were observed with the higher dose of vasopressin, but not with either dose of oxytocin. The effect of i.c.v. injection of clonidine (30 nmol), oxytocin (80 nmol) or vasopressin (40 nmol) was partially inhibited by prior i.c.v. injection of idazoxan (160, 320 nmol). The results suggest that the inhibition of 1.5% NaCl intake induced by i.c.v. injection of neuropeptides in sodium-depleted rats depends, in part, on the activation of central alpha(2)-adrenoceptors. (C) 1997 Elsevier B.V. B.V. All rights reserved.

Antagonism of clonidine injected intracerebroventricularly in different models of salt intake

Clonidine, an alpha 2-adrenergic agonist, injected into the brain inhibits salt intake of animals treated by the diuretic model of sodium depletion. In the present study, we address the question of whether central injection of clonidine also inhibits salt intake in animals deprived of water or in the need-free state. Saline or clonidine (30 nmol) was injected into the anterior third ventricle of 24-h sodium-depleted (furosemide + removal of ambient sodium), of 24-h water-deprived and of normovolemic (need-free state) adult male rats, Clonidine injected intracerebroventricularly (icv) inhibited the 1.5% NaCl intake for 120 min by 50 to 90% in every model tested. Therefore, different models of salt intake are inhibited by icv injection of clonidine, Idazoxan, an alpha 2-adrenergic antagonist, injected icy at a dose of 160 nmol, inhibited the effect of clonidine only in the furosemide + removal of ambient sodium model of salt intake. This indicates that the antagonism of this effect by idazoxan is dependent on the body fluid/sodium status of the animal.

ANTINOCICEPTIVE EFFECT OF AMITRAZ IN MICE AND RATS

Amitraz, a formamidine insecticide and acaricide used in veterinary practice, presents side effects related to its pharmacological activity on az-adrenergic receptors. The present study was undertaken to investigate the antinociceptive effect of amitraz in rats and mice. The tail-flick test was used to determine the duration of the antinociceptive effect of the intraperitoneal tip) administration of amitraz (1 and 2 mg/kg, 10 animals per group) in male Wistar rats weighing 180-220 g. The writhing test (using 10 ml/kg of a 0.6% acetic acid solution as a painful stimulus). was performed in 140 male Swiss mice weighing 20-30 g, divided into 14 groups that received ip injections of saline, amitraz (0.5, 1.0, 1.5, 2.0 and 4.0 mg/kg), xylazine or detomidine (1.0, 1.5, 2.0 and 4.0 mg/ kg), in order to compare the effect of amitraz to that caused by xylazine and detomidine, and to investigate the participation of alpha(2)-adrenergic receptors which were blocked by idazoxan (1 mg/kg). Amitraz induced a significant antinociceptive effect in both rats and mice. This effect is blocked in mice by idazoxan.

Ibotenate lesion of the medial hypothalamus alters the salt intake and pressor responses to activation of the median preoptic nucleus in rats

We investigated the influence of ibotenic acid lesions of the medial hypothalamus (MH) on salt appetite and arterial blood pressure responses induced by angiotensinergic and adrenergic stimulation of the median preoptic nucleus (MnPO) of rats. Previous injection of the adrenergic agonists norepinephrine, clonidine, phenylephrine, and isoproterenol into the MnPO of sham MH-lesioned rats caused no change in the sodium intake induced by ANG II. ANG II injected into the MnPO of MH-lesioned rats increased sodium intake compared with sham-lesioned rats. Previous injection of clonidine and isoproterenol increased, whereas phenylephrine abolished the salt intake induced by ANG II into the MnPO of MH-lesioned rats. Previous injection of norepinephrine and clonidine into the MnPO of sham MH-lesioned rats caused no change in the mean arterial pressure (MAP) induced by ANG II. Under the same conditions, previous injection of phenylephrine increased, whereas isoproterenol reversed the increase in MAP induced by angiotensin II (ANG II). ANG II injected into the MnPO of MH-lesioned rats induce a decrease in MAP compared with sham-lesioned rats. Previous injection of phenylephrine or norepinephrine into the MnPO of MH-lesioned rats induced a negative MAP, whereas pretreatment with clonidine or isoproterenol increased the MAP produced by ANG II injected into the MnPO of sham- or MH-lesioned rats. These data show that ibotenic acid lesion of the MH increases the sodium intake and presser responses induced by the concomitant angiotensinergic, alpha(2) and beta adrenergic activation of the MnPO, whereas alpha(1) activation may have opposite effects. MH involvement in excitatory and inhibitory mechanisms related to sodium intake and MAP control is suggested.

Low triioothyronine (T-3) or reverse triioothyronine (rT(3)) syndrome modifies gene expression in rats with congestive heart failure

Heart failure (NF) is frequently associated with euthyroid sicksyndrome (low T-3 and elevated rT(3)). We investigated if altered thyroid hormone in HF could affect expression of the TH receptor (TR alpha 1), and alpha and beta myosin heavy chains (alpha-MHC beta-MHC). HF was provoked in rats by aortic stenosis. We showed that rT(3) generated front liver and kidney deiodination significantly increased and T-3 decreased in HE; there was significantly higher TR alpha 1 expression, no alpha-MHC expression, but beta-MHC expression. Changes in TR alpha 1 could be compensating for low T-3 from HF.

Triiodothyronine mimics the effects of estrogen in breast cancer cell lines

MCF-7 (estrogen receptor positive - ER(+)) and MDA-MB-231 (estrogen receptor negative - ER(-)) are human breast cancer cell lines which express functional thyroid hormone receptors (c-erb A alpha 1 and c-erb beta 1) as indicated by stimulation of mitochondrial alpha-glycerophosphate dehydrogenase. In MCF-7, mimicking E(2), T-3 stimulated growth in a dose-dependent (10(10) M-10(-8) M) manner, induced the expression of progesterone receptor and growth factor TGF alpha mRNAs and inhibited that of TGF beta mRNA; T-3 also increased progesterone binding and LDH5 isozyme activities. None of these effects were observed in (ER(-)) MDA-MB-231 cells. 10(-6) M tamoxifen (TAM) reverted growth stimulation, suppressed progesterone receptor and TGF alpha mRNA induction and restored TGF beta mRNA to control levels in T-3-treated MCF-7 cells. That T-3 is acting in MCF-7 cells via its binding to ER is suggested by the immunoprecipitation of pre-bound I-125-T-3 from MCF-7 nuclear extracts by an ER-specific monoclonal antibody and by the displacement of H-3-estradiol binding to ER by radioinert T-3. Copyright (C) 1996 Elsevier B.V. Ltd.

Antidiarrheal mechanism of Carpolobia lutea leaf fractions in rats

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

Sedação com sufentanil e clonidina em pacientes submetidos a cateterismo cardíaco

FUNDAMENTO: A sedação para a realização de cateterismo cardíaco tem sido alvo de preocupação. Benzodiazepínicos, agonistas alfa-2 adrenérgicos e opioides são utilizados para esse fim, entretanto, cada um destes medicamentos possui vantagens e desvantagens. OBJETIVO: Avaliar a eficácia do sufentanil e da clonidina como sedativos em pacientes submetidos a cateterismo cardíaco, observando o impacto dos mesmos sobre os parâmetros hemodinâmicos e respiratórios, a presença de efeitos colaterais, além da satisfação do paciente e do hemodinamicista com o exame. MÉTODOS: Trata-se de um ensaio clínico prospectivo, duplo-cego, randomizado e controlado, que envolveu 60 pacientes que receberam 0,1 µg/kg de sufentanil ou 0,5 µg/kg de clonidina antes da realização do cateterismo cardíaco. O escore de sedação segundo a escala de Ramsay, a necessidade de utilização de midazolam, os efeitos colaterais, os parâmetros hemodinâmicos e respiratórios foram registrados, sendo os dados analisados em 06 diferentes momentos. RESULTADOS: O comportamento da pressão arterial, da frequência cardíaca e da frequência respiratória foi semelhante nos dois grupos, entretanto, no momento 2, os pacientes do grupo sufentanil (Grupo S) apresentaram menor escore de sedação segundo a escala de Ramsay, e a saturação periférica da oxihemoglobina foi menor que o grupo clonidina (Grupo C) no momento 6. Os pacientes do Grupo S apresentaram maior incidência de náusea e vômito pós-operatório que os pacientes do Grupo C. A satisfação dos pacientes foi maior no grupo clonidina. Os hemodinamicistas mostraram-se satisfeitos nos dois grupos. CONCLUSÃO: O sufentanil e a clonidina foram efetivos como sedativos em pacientes submetidos a cateterismo cardíaco. (Arq Bras Cardiol. 2011; [online].ahead print, PP.0-0)