Enhanced airways responsiveness in rats depleted of sensory neuropeptides by neonatal capsaicin treatment

This study aimed to investigate the in vivo and in vitro reactivity of airway smooth muscle in rats depleted of sensory neuropeptides by treatment with capsaicin at neonatal stage. Wistar rats were neonatally injected with either capsaicin (50 mg/kg, s.c., 2nd day of life) or its vehicle (10% ethanol and 10% Tween 80, in 0.9% w/v NaCl solution) and used at adult ages (60-70 days later). Analysis of the lungs showed a higher number of infiltrating neutrophils, eosinophils and mononuclear cells into the peribronchiolar regions of capsaicin-pretreated rats compared to vehicle group. This was associated with a higher contraction index of bronchiolar wall in the capsaicin group. The in vitro tracheal reactivity in response to methacholine (full muscarinic agonist) and pilocarpine (partial muscarinic agonist) was also significantly higher in capsaicin-pretreated rats compared to vehicle group. In conclusion, the neuropeptide depletion by capsaicin neonatal treatment lead to marked contraction of the rat airways at adult age, suggesting a protective role for C fibers in the lungs. (C) 2003 Elsevier B.V. Ireland Ltd. All rights reserved.

Influence of physical preconditioning on the responsiveness of rat pulmonary artery after pulmonary ischemia/reperfusion

The aim of this work was to evaluate the effect of physical preconditioning in the responsiveness of rat pulmonary rings submitted to lung ischemia/reperfusion (IR). Wistar rats were divided into three groups: Sedentary sham-operated (SD/SHAM); sedentary submitted to ischemia/reperfusion (SD/IR) and trained submitted to ischemia/reperfusion (TR/IR) animals. Exercise training consisted in sessions of 60 min/day running sessions, 5 days/week for 8 weeks. Left pulmonary IR was performed by occluding for 90 min and reperfusing for 120 min. After that, pulmonary arteries were isolated and concentration-response curves to acetylcholine (ACh), histamine (HIST), sodium nitroprusside (SNP), phenylephrine and U46619 were obtained. Neither potency (- log EC50) nor maximal responses (Emax) were modified for ACh and HIST in all groups. On the other hand, the potency for SNP was significantly increased in TR/IR group (8.23 ± 0.06) compared to SD/IR group (7.85 ± 0.04). Contractile responses mediated by a-adrenergic receptor were markedly decreased in IR groups (SD/IR: 6.75 ± 0.06 and TR/IR: 6.62 ± 0.04) compared to SD/SHAM (7.33 ± 0.05). No changes were seen for the U46619 in all groups. In conclusion, the present study shows that exercise training has no protective actions in the local blood vessel where the IR process takes place. © 2006 Elsevier Inc. All rights reserved.

VEGF-C expression in oral cancer by neurotransmitter-induced activation of beta-adrenergic receptors

The aim of this study was to investigate the expression of vascular endothelial growth factor type C (VEGF-C) in oral squamous cell carcinoma (OSCC) cell lines through norepinephrine-induced activation of beta-adrenergic receptors. Human OSCC cell lines (SCC-9 and SCC-25) expressing beta-adrenergic receptors were stimulated with different concentrations of norepinephrine (0.1, 1, and 10 μM) and 1 μM of propranolol, and analyzed after 1, 6, and 24 h. VEGF-C gene expression and VEGF-C production in the cell supernatant were evaluated by real-time PCR and by ELISA, respectively. The results showed that beta-adrenergic receptor stimulation by different concentrations of norepinephrine or blocking by propranolol did not markedly alter VEGF-C expression by SCC-9 and SCC-25 cells. VEGF-C protein levels produced by oral malignant cell lines after stimulation with different norepinephrine concentrations or blocking with propranolol was statistically similar (p > 0.05) to those of the control group (nonstimulated OSCC cell lines). Our findings suggest that stimulation of beta-adrenergic receptors by means of norepinephrine does not seem to modulate the VEGF-C expression in OSCC cell lines. These findings reinforce the need for further studies in order to understand the responsiveness of oral cancer to beta-adrenergic receptor stimulation or blockage, especially with regard to VEGF-C production. © 2012 International Society of Oncology and BioMarkers (ISOBM).

Cardiac dysfunction induced by obesity es not related to beta-adrenergic system impairment at the receptor-signalling pathway

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

Responsiveness of the interrenal tissue of Jundia (Rhamdia quelen) to an in vivo ACTH test following acute exposure to sublethal concentrations of agrichemicals

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Venous tone and cardiac function in the South American rattlesnake Crotalus durissus: mean circulatory filling pressure during adrenergic stimulation in anaesthetised and fully recovered animals

The effects of adrenergic stimulation on mean circulatory filling pressure (MCFP), central venous pressure (P-CV) and stroke volume (Vs), as well as the effects of altered MCFP through changes of blood volume were investigated in rattlesnakes (Crotalus durissus). MCFP is an estimate of the upstream pressure driving blood towards the heart and is determined by blood volume and the activity of the smooth muscle cells in the veins (venous tone). MCFP can be determined as the plateau in P-CV during a total occlusion of blood flow from the heart.Vs decreased significantly when MCFP was lowered by reducing blood volume in anaesthetised snakes, whereas increased MCFP through infusion of blood (up to 3 ml kg(-1)) only led to a small rise in Vs. Thus, it seems that end-diastolic volume is not affected by an elevated MCFP in rattlesnakes. To investigate adrenergic regulation on venous tone, adrenaline as well as phenylephrine and isoproterenol (alpha- and beta-adrenergic agonists, respectively) were infused as bolus injections (2 and 10 mu g kg(-1)). Adrenaline and phenylephrine caused large increases in MCFP and P-CV, whereas isoproterenol decreased both parameters. This was also the case in fully recovered snakes. Therefore, adrenaline affects venous tone through both alpha- and beta-adrenergic receptors, but the alpha-adrenergic receptor dominates at the dosages used in the present study. Injection of the nitric oxide donor SNP caused a significant decrease in P-CV and MCFP. Thus, nitric oxide seems to affect venous tone.

The adrenergic regulation of the cardiovascular system in the South American rattlesnake, Crotalus durissus

The present study investigates adrenergic regulation of the systemic and pulmonary circulations of the anaesthetised South American rattlesnake, Crotalus durissus. Haemodynamic measurements were made following bolus injections of adrenaline and adrenergic antagonists administered through a systemic arterial catheter. Adrenaline caused a marked systemic vasoconstriction that was abolished by phentolamine, indicating this response was mediated through alpha-adrenergic receptors. Injection of phentolamine gave rise to a pronounced vasodilatation (systemic conductance (G(sys)) more than doubled), while injection of propranolol caused a systemic vasoconstriction, pointing to a potent alpha-adrenergic, and a weaker beta-adrenergic tone in the systemic vasculature of Crotalus. Overall, the pulmonary vasculature was far less responsive to adrenergic stimulation than the systemic circulation. Adrenaline caused a small but non-significant pulmonary vasodilatation and there was tendency of reducing this dilatation after either phentolamine or propranolol. Injection of phentolamine increased pulmonary conductance (G(pul)), while injection of propranolol produced a small pulmonary constriction, indicating that alpha-adrenergic and beta-adrenergic receptors contribute to a basal regulation of the pulmonary vasculature. Our results suggest adrenergic regulation of the systemic vasculature, rather than the pultrionary, may be an important factor in the development of intracardiac shunts. (c) 2007 Elsevier B.V. All rights reserved.

Prognostic significance of beta-2 adrenergic receptor in oral squamous cell carcinoma

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Disfunção miocárdica e alterações no trânsito de cálcio intracelular em ratos obesos

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

Administration of beta(2)-adrenergic agonists during the peri-implantation period does not improve implantation or pregnancy rates in intracytoplasmic sperm injection (ICSI) cycles

Purpose: the objective of the present investigation was to determine implantation and pregnancy rates in patients undergoing ICSI and treated with beta(2)-adrenergic agonists, considering the uterine-relaxing action of these agents.Methods: A total of 225 women undergoing ICSI at the Center for Human Reproduction, Sinha Junqueira Maternity Foundation, entered the study. Patient participation in each group was random, by drawing lots, using a randomization table previously elaborated for the study (2:2:1). The group I (90 women) received 10 mg of terbutaline daily for 15 days starting on the day of oocyte retrieval; group II (90 women) received 20 mg of ritodrine daily during the same period of time as group I; group III (45 patients) received no treatment and was used as control. The evaluation was interrupted in 3 patients of group I and in 30 patients of group II because of a high incidence of side effects.Results: Pregnancy, implantation, and miscarriage rates were not significantly different (p>0.05) between the three groups: 29.88%, 13.25%, and 26.9% for group I; 33.33%, 17.5%, and 10.0% for group II; 28.88%, 15.07%, and 15.38% for group III, respectively.Conclusions: the results of this study do not support the routine use of beta(2)-adrenergic agonists during the peri-implantation period in assisted reproductive technology cycles.

Involvement of forebrain imidazoline and alpha(2)-adrenergic receptors in the antidipsogenic response to moxonidine

We investigated the participation of central alpha(2)-adrenoceptors and imidazoline receptors in the inhibition of water deprivation-induced water intake in rats. The alpha(2)-adrenoceptor and imidazoline antagonist idazoxan (320 nmol), but not the alpha(2)-adrenoceptor antagonist yohimbine, abolished the antidipsogenic effect of moxonidine (alpha(2)-adrenoceptor and imidazoline agonist, 20 nmol) microinjected into the medial septal area. Yohimbine abolished the antidipsogenic effect of moxonidine intracerebroventricularly. Therefore, central moxonidine may inhibit water intake acting independently on both imidazoline receptors and alpha(2)-adrenoceptors at different forebrain sites.

Central alpha(2) adrenergic receptors and cholinergic-induced salivation in rats

Salivation induced by intraperitoneal (i.p.) injections of pilocarpine (cholinergic agonist) is reduced by intracerebroventricular (i.c.v.) injections of moxonidine (alpha(2) adrenergic and imidazoline receptor agonist). In the present study, we investigated the involvement of central alpha(2) adrenergic receptors in the inhibitory effect of i.c.v. moxonidine on i.p. pilocarpine-induced salivation. Male Holtzman rats with stainless steel cannula implanted into the lateral ventricle (LV) were used. Saliva was collected using pre-weighted small cotton balls inserted into the animal's mouth under ketamine (100 mg kg(-1)) anesthesia. Salivation was induced by i.p. injection of pilocarpine (4 mu mol kg(-1)). Pilocarpine-induced salivation was reduced by i.c.v. injection of moxonidine (10 nmol) and enhanced by i.c.v. injections of either RX 821002 (160 nmol) or yohimbine (320 nmol). The inhibitory effect of i.c.v. moxonidine on pilocarpine-induced salivation was abolished by prior i.c.v. injections of the alpha(2) adrenergic receptor antagonists, RX 821002 (160 nmol) or yohimbine (160 and 320 nmol). The alpha(1) adrenergic receptor antagonist prazosin (320 nmol) injected i.c.v. did not change the effect of moxonidine on pilocarpine-induced salivation. The results suggest that moxonidine acts on central alpha(2) adrenergic receptors to inhibit pilocarpine-induced salivation, and that this salivation is tonically inhibited by central alpha(2) adrenergic receptors. (C) 2002 Elsevier B.V. All rights reserved.

Activation of alpha(2)-adrenergic receptors into the lateral parabrachial nucleus enhances NaCl intake in rats

Water and NaCl intake is strongly inhibited by the activation of alpha(2)-adrenergic receptors with clonidine or moxonidine (alpha(2)-adrenergic/imidazoline agonists) injected peripherally or into the forebrain and by serotonin and cholecystokinin in the lateral parabrachial nucleus (LPBN). Considering that alpha(2)-adrenergic receptors exist in the LPBN and the similar origin of serotonergic and adrenergic afferent pathways to the LPBN, in this study we investigated the effects of bilateral injections of moxonidine alone or combined with RX 821002 (alpha(2)- adrenergic antagonist) into the LPBN on 1.8% NaCl and water intake induced by the treatment with s.c. furosemide (10 mg/kg)+captopril (5 mg/kg). Additionally, we investigated if moxonidine into the LPBN would modify furosemide+captopril-induced c-fos expression in the forebrain. Male Holtzman rats with cannulas implanted bilaterally in the LPBN were used. Contrary to forebrain injections, bilateral LPBN injections of moxonidine (0.1, 0.5 and 1 nmol/0.2 mul) strongly increased furosemide+captopril-induced 1.8% NaCl intake (16.6 +/- 2.7, 44.5 +/- 3.2 and 44.5 +/- 4.3 ml/2 h, respectively, vs. vehicle: 6.9 +/- 1.5 ml/2 h). Only the high dose of moxonidine increased water intake (23.3 +/- 3.8 ml/2 h, vs. vehicle: 12.1 +/- 2.6 ml/2 h). Prior injections of RX 821002 (10 and 20 nmol/0.2 mu1) abolished the effect of moxonidine (0.5 nmol) on 1.8% NaCl intake. Moxonidine into the LPBN did not modify furosemide+captopril-induced c-fos expression in forebrain areas related to the control of fluid-electrolyte balance. The results show that the activation of LPBN a2-adrenergic receptors enhances furosemide+captopril-induced 1.8% NaCl and water intake. This enhancement was not related to prior alteration in the activity of forebrain areas as suggested by c-fos expression. Previous and present results indicate opposite roles for alpha(2-)adrenergic receptors in the control of sodium and water intake according to their distribution in the rat brain. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.