Feocromocitoma quístico gigante: reporte de un caso / Pheochromocytoma giant cystic: a case report

El feocromocitoma quístico gigante es tumor adrenal raro en el que predomina el curso asintomático; por lo que muchos de los casos no son diagnosticados hasta el momento de la cirugía. La simple movilización del tumor se asocia con el paso a la sangre de grandes cantidades de catecolaminas y a una elevada morbimortalidad.; por esta razón la cirugía per se y su manejo perioperatorio constituyen un enorme desafío. En este artículo se presenta el caso de un feocromocitoma gigante maligno (35 cm) que ocupaba todo el hemiabdomen derecho. Aun con el diagnóstico preoperatorio de feocromocitoma, el bloqueo farmacológico preoperatorio y las medidas intraoperatorias, el paciente falleció poco antes de que finalizara la cirugía.

The giant cystic pheochromocytoma is a rare adrenal tumor in the predominantly asymptomatic course; so many cases are not diagnosed until the time of surgery. The simple mobilization of the tumor is associated with the passage to the blood of large amounts of catecholamines and high morbidity and mortality. So the surgery itself and perioperative management are a huge challenge. This article describes the case of a malignant giant pheochromocytoma (35 cm) which occupied the entire right abdomen. Even with the preoperative diagnosis of pheochromocytoma, pharmacological blockade preoperative and intraoperative measures, the patient died shortly before the end of surgery.

[Pheochromocytoma giant cystic: a case report]. / Feocromocitoma quístico gigante: reporte de un caso.

The giant cystic pheochromocytoma is a rare adrenal tumor in the predominantly asymptomatic course; so many cases are not diagnosed until the time of surgery. The simple mobilization of the tumor is associated with the passage to the blood of large amounts of catecholamines and high morbidity and mortality. So the surgery itself and perioperative management are a huge challenge. This article describes the case of a malignant giant pheochromocytoma (35 cm) which occupied the entire right abdomen. Even with the preoperative diagnosis of pheochromocytoma, pharmacological blockade preoperative and intraoperative measures, the patient died shortly before the end of surgery.

Mirtazapine prevents induction and expression of cocaine-induced behavioral sensitization in rats.

Cocaine abuse is a major health problem worldwide. Treatment based on both 5-HT2A/C and 5-HT3 receptor antagonists attenuate not only the effects of cocaine abuse but also the incentive/motivational effect related to cocaine-paired cues. Mirtazapine, an antagonist of postsynaptic α2-adrenergic, 5-HT2A/C and 5HT3 receptors and inverse agonist of the 5-HT2C receptor, has been shown to effectively modify, at the preclinical and clinical levels, various behavioral alterations induced by drugs abuse. Therefore, it is important to assess whether chronic dosing of mirtazapine alters locomotor effects of cocaine as well as induction and expression of cocaine sensitization. Our results reveal that a daily mirtazapine regimen administered for 30days effectively induces a significant attenuation of cocaine-dependent locomotor activity and as well as the induction and expression of behavioral sensitization. These results suggest that mirtazapine may be used as a potentially effective therapy to attenuate induction and expression of cocaine-induced locomotor sensitization.

Both α1- and α2-adrenoceptors in the insular cortex are involved in the cardiovascular responses to acute restraint stress in rats.

The insular cortex (IC) is a limbic structure involved in cardiovascular responses observed during aversive threats. However, the specific neurotransmitter mediating IC control of cardiovascular adjustments to stress is yet unknown. Therefore, in the present study we investigated the role of local IC adrenoceptors in the cardiovascular responses elicited by acute restraint stress in rats. Bilateral microinjection of different doses (0.3, 5, 10 and 15 nmol/100 nl) of the selective α1-adrenoceptor antagonist WB4101 into the IC reduced both the arterial pressure and heart rate increases elicited by restraint stress. However, local IC treatment with different doses (0.3, 5, 10 and 15 nmol/100 nl) of the selective α2-adrenoceptor antagonist RX821002 reduced restraint-evoked tachycardia without affecting the pressor response. The present findings are the first direct evidence showing the involvement of IC adrenoceptors in cardiovascular adjustments observed during aversive threats. Our findings indicate that IC noradrenergic neurotransmission acting through activation of both α1- and α2-adrenoceptors has a facilitatory influence on pressor response to acute restraint stress. Moreover, IC α1-adrenoceptors also play a facilitatory role on restraint-evoked tachycardiac response.

[Laparoscopic adrenalectomy: the best surgical option]. / Suprarrenalectomia laparoscópica: la mejor opción de tratamiento quirúrgico.

BACKGROUND: Laparoscopic approach has become the gold standard for the surgical treatment of suprarenal gland. Nevertheless there is still controversy about the laparoscopic treatment of adrenal carcinoma. MATERIAL AND METHODS: From April 2005 to April 2012, 37 laparoscopic adrenalectomies were performed. We describe and analyze retrospectively: age, sex, side, indication for surgery, tumor size, length of hospital stay, complications and conversion rate. RESULTS: 37 Patients, 19 male and 18 female, aged 51.72 ± 14.42 years, were operated on between 2005 and 2012. Twenty-two left-sided lesions (59.45%) and 15 right-sided lesions (40.54%) were operated on. The indications for surgery were non-functioning adenoma larger than 4 cm or rapid growth and hormone-secreting tumours. The diagnosis was confirmed in all the cases with computed tomography and or magnetic resonance imaging and also metaiodobenzylguanidine scintigraphy if pheochromocytoma was suspected. In all the cases we realized a complete pre-operative hormonal study. CONCLUSIONS: Laparoscopic adrenalectomy is a safe procedure and gold standard technique for suprarenal surgery. Our experience is very satisfactory, with comparable results to the reference standard open approach.

Antecedentes: la vía de acceso laparoscópico es la técnica de elección en el tratamiento quirúrgico de la glándula suprarrenal, excepto del carcinoma suprarrenal. Objetivo: revisar nuestra experiencia en suprarrenalectomías laparoscópicas por vía lateral transperitoneal efectuadas entre los años 2005 y 2012. Material y método: estudio descriptivo y retrospectivo efectuado mediante la revisión de historias clínicas de 37 pacientes con diagnóstico, al alta, de tumor adrenal y a quienes se hizo adrenalectomía laparoscópica entre abril de 2005 y abril de 2012. Se consideraron los siguientes datos: edad, sexo, lateralidad, indicación quirúrgica, resultados anatomopatológicos, tamaño de la lesión, estancia hospitalaria, tasa de conversión y complicaciones perioperatorias. Resultados: durante el periodo de estudio se intervinieron 37pacientes (19 varones y 18 mujeres) con edad media de 51.72 ± 14.42 años. Se realizaron 22adrenalectomías izquierdas (59.45%) y 15 derechas (40.54%). Las indicaciones de suprarrenalectomía fueron: incidentaloma mayor de 4 cm o con crecimiento rápido y tumores productores de hormonas. El diagnóstico se confirmó con tomografía computada, resonancia magnética, o ambas, y con gammagrafía metaiodobencilguanidina en el caso de sospecha de feocromocitoma y estudio hormonal completo en todos los pacientes. Conclusiones: la suprarrenalectomía laparoscópica sigue siendo la técnica de elección en el tratamiento de pacientes con afectación de la glándula suprarrenal porque ha demostrado ser segura y eficaz, como quedó confirmado en nuestra serie, que tuvo resultados similares a los de la bibliografía.

Possible mechanisms of action of the aqueous extract of Artocarpus altilis (breadfruit) leaves in producing hypotension in normotensive Sprague-Dawley rats.

CONTEXT AND OBJECTIVES: Artocarpus altilis (Parkinson) Fosberg (Moraceae) (breadfruit) leaves are used as an antihypertensive remedy. We investigated the possible mechanisms of action of its aqueous extract and its effect on cytochromes P450 (CYP) enzyme activities. MATERIALS AND METHODS: Intravenous administration of an aqueous leaf extract (20.88-146.18 mg/kg) of A. altilis on mean arterial pressure and heart rate were recorded via cannulation of the carotid artery on anaesthetized normotensive Sprague-Dawley rats. Recordings of the contractile activity of the aortic rings to the extract (0.71-4.26 mg/mL) were studied using standard organ bath techniques. Inhibitions of human CYP3A4 and CYP2D6 enzyme activities were evaluated by means of a fluorometric assay in 96 well plates using heterologously expressed microsomes. RESULTS: A. altilis caused significant (p < 0.05) hypotensive and bradycardiac responses unaffected by atropine (2 mg/kg) and mepyramine (5 mg/kg), but attenuated by propranolol (1 mg/kg) and N(G)-nitro-L-arginine methyl ester (5 mg/kg). The extract (0.71-4.26 mg/mL) significantly (p < 0.05) relaxed phenylephrine (10⁻9-10⁻4 M) and 80 mM KCl-induced contractions in endothelium intact and denuded aortic rings; and caused a significant (p < 0.05) rightward shift of the Ca²âº dose-response curves in Ca²âº-free Kreb's solution. Moderate inhibitions of cytochrome P450s (CYP3A4 and CYP2D6) enzyme activities with IC50 values of 0.695 ± 0.187 and 0.512 ± 0.131 mg/mL, respectively, were produced. CONCLUSION: A. altilis exhibits negative chronotropic and hypotensive effects through α-adrenoceptor and Ca²âº channel antagonism. Drug adversity effects are unlikely if the aqueous leaf extract is consumed with other medications reliant on CYP3A4 and CYP2D6 metabolism. This study thus provides scientific evidence for the use of the breadfruit in the treatment of hypertension.

Subarachnoid serotonergic and noradrenergic antagonists increase the pain response in rats.

BACKGROUND AND OBJECTIVES: There is evidence that the passage of nociceptive information through the posterior horn of the spinal cord (PHSC) on its way to rostral levels of the central nervous system undergoes profound excitatory and inhibitory influences. The objective of the present study was to compare the effects of the subarachnoid administration of methysergide, phentolamine, and phentolamine associated with methysergide on phases I, intermediate, and II of the modified formalin test in rats. METHODS: Twenty-eight male Wistar rats distributed randomly in four groups (n=7) to received subarachnoid saline solution (GC), phentolamine (GF), methysergide (GM), or phentolamine associated with methysergide (GFM). Pain was induced by the administration of formalin in the dorsal region of the right hind paw. The test was divided in three phases: phase I, intermediate, and phase II. Statistical analysis of the results was performed using the software SPSS (Statistical Package for Social Sciences), adopting a level of significance of 5%. RESULTS: In the intermediate phase the number of paw elevations was significantly higher in GF, GM, and GFM groups when compared to the GC group. CONCLUSIONS: The results suggest the existence of a noradrenergic and serotonergic effect in the inhibitory descending system of acute pain, with the possibility of using serotonergic and α1-adrenergic antagonists to control acute pain.

Antagonistas serotoninérgico e noradrenérgico por via subaracnoidea aumentam a resposta álgica em ratos / Subarachnoid serotonergic and noradrenergic antagonists increase the pain response in rats

JUSTIFICATIVA E OBJETIVOS: Há evidências de que a passagem de informações nociceptivas pelo corno posterior da medula espinhal (CPME) seguindo para níveis rostrais do sistema nervoso central sofre profundas influências excitatórias e inibitórias. A presente pesquisa teve como objetivo comparar os efeitos da metissergida, da fentolamina e da fentolamina associada à metissergida, administrados por via subaracnoidea, sobre as fases I, intermediária e II do teste da formalina modificado em ratos. MÉTODO: Foram utilizados 28 ratos Wistar machos, distribuídos aleatoriamente em quatro grupos (n = 7) para receber solução salina (GC), fentolamina (GF), metissergida (GM) ou fentolamina associada à metissergida (GFM) por via subaracnoidea. A dor foi induzida pela administração de formalina na região dorsal da pata posterior direita. O teste foi dividido em três fases; fase I, intermediária e fase II. A análise estatística dos resultados foi realizada utilizando o programa SPSS (Statistical Package for Social Sciences), adotando o nível de significância de 5 por cento. RESULTADOS: Na fase intermediária, o número de elevações da pata foi significativamente maior nos grupos GF, GM e GFM quando comparados com o grupo GC. CONCLUSÕES: Os resultados sugerem a existência de efeito noradrenérgico e serotoninérgico no sistema inibitório descendente da dor aguda, com a possibilidade de emprego de agonistas serotoninérgicos e α1-adrenérgicos para controle da dor aguda.

BACKGROUND AND OBJECTIVES: There is evidence that the passage of nociceptive information through the posterior horn of the spinal cord (PHSC) on its way to rostral levels of the central nervous system undergoes profound excitatory and inhibitory influences. The objective of the present study was to compare the effects of the subarachnoid administration of methysergide, phentolamine, and phentolamine associated with methysergide on phases I, intermediate, and II of the modified phormaline test in rats. METHODS: Twenty-eight male Wistar rats distributed randomly in four groups (n = 7) to received subarachnoid saline solution (GC), phentolamine (GF), methysergide (GM), or phentolamine associated with methysergide (GFM). Pain was induced by the administration of phormaline in the dorsal region of the right hind paw. The test was divided in three phases: phase I, intermediate, and phase II. Statistical analysis of the results was performed using the software SPSS (Statistical Package for Social Sciences), adopting a level of significance of 5 percent. RESULTS: In the intermediate phase the number of paw elevations was significantly higher in GF, GM, and GFM groups when compared to the GC group. CONCLUSIONS: The results suggest the existence of a noradrenergic and serotonergic effect in the inhibitory descending system of acute pain, with the possibility of using serotonergic and α1-adrenergic antagonists to control acute pain.

JUSTIFICATIVA Y OBJETIVOS: Existen evidencias de que el paso de informaciones nociceptivas por el cuerno posterior de la médula espinal (CPME), y que continúa hacia niveles rostrales del sistema nervioso central, sufre profundas influencias excitatorias e inhibitorias. La presente investigación quiso comparar los efectos de la metisergida, de la fentolamina y de la fentolamina asociada a la metisergida, administrados por vía subaracnoidea, sobre las fases I, intermedia y II del test de la formalina modificado en ratones. MÉTODO: Fueron utilizados en el experimento, 28 ratones Wistar machos, distribuidos aleatoriamente en cuatro grupos (n = 7), para recibir una solución salina (GC), fentolamina (GF), metisergida (GM) o fentolamina asociada a la metisergida ((GFM). El dolor fue inducido por la administración de formalina en la región dorsal de la pata posterior derecha. El test fue dividido en tres fases: fase I, intermedia y fase II. El análisis estadístico de los resultados fue hecho utilizando el programa SPSS (Statistical Package for Social Sciences), [Paquete Estadístico para las Ciencias Sociales], adoptando el nivel de significancia de un 5 por ciento. RESULTADOS: En la fase intermedia, el número de elevaciones de la pata fue significativamente mayor en los grupos GF, GM y GFM cuando se comparó con el grupo GC. CONCLUSIONES: Los resultados nos sugieren la existencia de un efecto noradrenérgico y serotoninérgico en el sistema inhibitorio descendiente del dolor agudo, con la posibilidad del uso de agonistas serotoninérgicos y α1-adrenérgicos para el control del dolor agudo.

The improvement of the anti-hyperalgesic effect of ketamine and of its isomers by the administration of ifenprodil.

Intrathecal or epidural administration of NMDA (N-methyl-D-aspartate) receptors antagonists, in special ketamine and ifenprodil are used to control moderate to severe hyperalgesia in humans. Activation of NMDA receptor usually requires binding of two agonists, glutamate and glycine, in different receptor subunits. Ketamine is a NMDA receptor antagonist and acts at phencyclidine site in NR1 subunit while ifenprodil is a selective NR2B subunit antagonist of NMDA receptor. The aim of this study was to investigate the pharmacological interactions between ketamine or its isomers and ifenprodil, when intrathecally co-administrated, to reduce prostaglandin E(2)-induced hyperalgesia in rat's hind paw. The intrathecal administration of ketamine, its isomers R(-) or S(+), or ifenprodil-induced anti-hyperalgesic effects in a dose-related manner. Ifenprodil, in a dose that did not induce significant effect when administrated alone, significantly improved the anti-hyperalgesic effect of ketamine or its isomers. The other way round, ketamine or S(+) ketamine, but not R(-) ketamine, in a dose that did not induce significant effect when administrated alone, improved the anti-hyperalgesic effect of ifenprodil. However, by comparing ED(50)s (half maximal effective doses), ifenprodil-induced potentiation of ketamine was significantly greater than ketamine-induced potentiation of ifenprodil. The findings of this present study suggest that intrathecal administration of very small doses of ifenprodil, just before and ketamine significantly improves its anti-hyperalgesic effect and this association could be useful to control inflammatory pain with less undesirable effects.

Reversible immobilization of giant otters (Pteronura brasiliensis) using medetomidine-ketamine and atipamezole.

This communication reports a partially reversible chemical immobilization protocol used for translocation and veterinary care in giant otter (Pteronura brasiliensis; GO). Six GOs (three males and three females) weighing 24.8 +/- 4.0 kg (mean +/- SD) and ranging in age from 16 to 42 mo old were anesthetized with an i.m. combination of medetomidine (29 +/- 3 microg/kg) and ketamine (3.9 +/- 0.4 mg/kg). To perform all procedures, two otters required an additional dose of ketamine (1.5 mg/kg). Anesthesia was reversed with atipamezole i.m. (147 +/- 14 mg/kg). The mean induction time and recovery times were 12 +/- 5 and 4 min (range, 0-9 min), respectively, with an anesthesia time of 47 +/- 16 min. According to these results, the combination of medetomidine (30 microg/kg i.m.) and ketamine (4 mg/kg i.m.) is a reasonable choice for inducing anesthesia in GOs.

Simultaneous blockade of alpha and beta adrenoceptors impairs cutaneous wound healing in rats.

BACKGROUND: Recent studies showed that propranolol administration (beta-antagonist), but not phentolamine administration (alpha-antagonist), delays cutaneous wound healing. However, alpha adrenoceptor activation may be participating in propranolol-induced alterations. OBJECTIVE: This study aims to investigate the effects of simultaneous blockade of beta and alpha adrenoceptors on cutaneous wound healing. METHODS: Rats were treated with propranolol plus phentolamine dissolved in water. An excisional lesion was done and measured. Lesions were formalin-fixed and paraffin-embedded 21 days after wounding. Sections were stained with haematoxylin and eosin, toluidine blue and Sirius red, and immunostained for alpha-smooth muscle actin or proliferating cell nuclear antigen. RESULTS: Administration of propranolol plus phentolamine reduced wound contraction and re-epithelialization, but increased cellular proliferation and the number of mast cells. There was no difference in myofibroblast density, collagen fibre organization and polymorphonuclear number between the control and treated groups. CONCLUSION: Simultaneous blockade of beta and alpha adrenoceptors impairs cutaneous wound healing. Furthermore, propranolol-induced impairment on cutaneous wound healing does not occur through alpha adrenoceptor activation.

The effects of dutasteride, tamsulosin, and the combination on storage and voiding in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the Combination of Avodart and Tamsulosin study.

This article reports the results of a post hoc analysis of the multicenter, randomized, double-blind Combination of Avodart and Tamsulosin (CombAT) study, which aimed to investigate the effects of dutasteride (0.5 mg), tamsulosin (0.4 mg), and their combination on storage and voiding symptoms in 4844 men aged > or =50 years with moderate-to-severe lower urinary tract symptoms (International Prostate Symptom Score > or =12), prostate volume (PV) > or =30 cm(3) and PSA 1.5-10 ng ml(-1). After 24 months, combination treatment achieved significantly greater mean reductions in both voiding and storage symptoms than either monotherapy, in each of the three baseline PV tertiles (30 to <42, 42 to <58, > or =58 cm(3)). Dutasteride was as effective as tamsulosin for control of storage symptoms, but provided significantly greater relief of voiding symptoms than tamsulosin.

Renal vasodilation induced by hypernatraemia: role of alpha-adrenoceptors in the median preoptic nucleus.

1. The renal vasodilation induced by infusion of hypertonic saline (HS) in anaesthetized rats has been shown to depend on the integrity of the median preoptic nucleus (MnPO), as well as noradrenergic afferents to this nucleus. In the present study, we sought to determine the role of alpha(1) and alpha(2)-adrenoceptors in the MnPO in cardiovascular responses induced by intravenous HS infusion (3 mol/L NaCl; 1.8 mL/kg, i.v., over 1 min). 2. Male Wistar rats (320-360 g) were anaesthetized with urethane (1.2 g/kg, i.v.) and instrumented for recording of mean arterial pressure (MAP), renal blood flow (RBF) and vascular conductance (RVC). In one experimental group, rats were injected with yohimbine, prazosin or saline (control) 20 min before HS infusion. In another experimental group, rats were injected with yohimbine or prazosin 20 min after HS infusion. 3. In control rats (n = 7), HS infusion 20 min after saline nanoinjection produced a transient hypertension. Ten minutes after HS infusion, RBF and RVC increased to 159 +/- 14% and 145 +/- 11% of baseline, respectively. Nanoinjection of the alpha(1)-adrenoceptor antagonist prazosin (0.25 mmol/L; n = 6) into the MnPO 20 min before HS infusion increased the HS-induced pressor response. However, HS-induced increases in RBF and RVC were significantly reduced (130 +/- 11% and 105 +/- 6% of baseline, respectively, 10 min after HS). Nanoinjection of the alpha(2)-adrenoceptor antagonist yohimbine (0.23 mmol/L; n = 5) into the MnPO 20 min before HS infusion increased the duration of the pressor response and reduced the increases in RBF and RVC induced by HS (117 +/- 10% and 97 +/- 11% of baseline, respectively, 10 min after HS). 4. We also observed that nanoinjections of the prazosin into the MnPO 60 min after HS infusion resulted in a gradual return of RBF and RVC to baseline values. However nanoinjection of yohimbine 60 min after HS failed to reduce renal vasodilatation induced by hypernatremia. 5. The results of the present study demonstrate that the integrity of adrenergic neurotransmission in the MnPO is essential for the renal vasodilation that follows acute increases in blood sodium concentration.

The synergistic interaction between morphine and maprotiline after intrathecal injection in rats.

BACKGROUND: Antidepressant drugs act as potent inhibitors of norepinephrine and/or serotonin reuptake and are widely used with opioids for the treatment of chronic pain. The mechanism of this increased analgesic action is unclear. We compared the antinociceptive effects of the intrathecal administration of morphine with that of a nonselective (amitriptyline) or selective (maprotiline or citalopram) antidepressant drug using the thermal withdrawal test in rats. We also investigated the possible mechanisms involved in the interactions of these drugs. METHODS: Male Wistar rats were anesthetized with sevoflurane and administered morphine and antidepressant drugs, or saline, through intrathecal injection. The antinociceptive effect was evaluated using the thermal withdrawal test before and after drug administration. The time for the withdrawal reaction was expressed as percentage of maximum possible effect (MPE). Animals were also pretreated with yohimbine (a nonselective alpha2-adrenergic antagonist) and naloxone (a nonselective opioid antagonist) for mechanism of action studies. Pharmacologic interaction was evaluated using isobolographic analysis of simultaneous administration of fixed proportions of maprotiline and morphine. RESULTS: Single intrathecal administration of morphine (2 microg), amitriptiline (125 microg), citalopram (144 microg), and maprotiline (1.25 microg) produced 51.6% +/- 8.9%, 10.3% +/- 3.2%, 33.8% +/- 5.2%, and 48.5% +/- 9.2% MPE, respectively. The antinociceptive effect of morphine was increased when combined with amitriptyline (91.3% +/- 4.6% MPE) and maprotiline (86.9% +/- 9.2% MPE) but not with citalopram (40.6% +/- 4.6% MPE). Coadministration of maprotiline increased the antinociceptive duration of morphine by 4-fold (from 120 to 480 min), which was reversed by pretreatment with the alpha-2 adrenoceptor inhibitor, yohimbine, and the mu-type opioid receptor antagonist, naloxone. Isobolographic analysis demonstrated a synergistic interaction between morphine and maprotiline. CONCLUSIONS: Selective norepinephrine reuptake inhibitors can significantly increase the intensity and duration of morphine antinociceptive activity via both alpha(2)-adrenergic and opioid receptors. This interaction was not observed with the selective serotonin inhibitor, citalopram.

Administration of noradrenaline in the autonomic ganglia modifies the testosterone release from the testis using an ex vivo system.

The male gonad receives nerve fibres from the autonomic ganglionic system. These fibres converge on the testis along two pathways, the superior and the inferior spermatic nerves. The superior spermatic nerve runs from the superior mesenteric ganglion alongside the testicular artery, whereas the inferior spermatic nerve originates in inferior mesenteric ganglion, accompanies the vas deferens and penetrates the inferior pole of the testis. The aim of this work was to evaluate androgen release after the addition of noradrenaline or adrenoreceptor antagonists (propranolol or phentolamine) to the ganglionic compartment. An ex vivo system used in a previous work was incubated in two separate containers, one for the testis and the other for the ganglion. Both organs remain interconnected (as in vivo) by the respective spermatic nerve. When noradrenaline was added to the inferior mesenteric ganglion, testosterone release in the gonad container underwent a progressive and significant increment. Propranolol diminishes and phentolamine increases the androgen release. When using the superior mesenteric ganglion, no changes were observed. These results indicate that the ganglionic stimulation of the autonomic system clearly participates in testosterone release from the testis. This effect depends on the ganglion involved. These results make it evident that not only the classical and well-known hypothalamus-hypophysial axis, but also the peripheral nervous system, via the autonomic ganglia, are directly involved in the endocrine control of the testis.

Bed nucleus of the stria terminalis alpha(1)-adrenoceptor modulates baroreflex cardiac component in unanesthetized rats.

The bed nucleus of stria terminalis (BST) has a tonic modulating role on the baroreflex parasympathetic component. In the present study, we verified that local BST-adrenoceptors modulate baroreflex-evoked bradycardiac responses in unanesthetized rats. Bilateral microinjection of the selective alpha(1)-adrenoceptor antagonist WB4101 (15 nmol/100 nL) into the BST increased the gain of reflex bradycardia in response to mean arterial pressure increases caused by intravenous (i.v.) infusion of phenylephrine, suggesting that BST alpha(1)-adrenoceptors modulate baroreflex bradycardiac response. Bilateral microinjection of either the selective alpha(2)-adrenoceptor antagonist RX821002 (15 nmol/100 nL) or the non-selective beta-adrenoceptor antagonist propranolol (15 nmol/100 nL) into the BST had not affected baroreflex bradycardia. Animals were pretreated intravenously with the cholinergic muscarinic receptor antagonist homatropine methyl bromide (HMB, 1.5 mg/Kg) to test the hypothesis that activation of alpha(1)-adrenoceptors in the BST would modulate the baroreflex parasympathetic component. Baroreflex bradycardiac responses evoked before and after BST treatment with WB4101 were no longer different when rats were pretreated with HMB. These results suggest that parasympathetic activation accounts for the effects saw after BST pharmacological manipulation and ruling out the possibility of a sympathetic withdraw. In conclusion, our data point out that local alpha(1)-adrenoceptors mediate the BST tonic influence on the baroreflex bradycardiac response modulating parasympathetic cardiac activity.

Blood pressure measurement with the tail-cuff method in Wistar and spontaneously hypertensive rats: influence of adrenergic- and nitric oxide-mediated vasomotion.

INTRODUCTION: Systolic blood pressure (SBP) is still measured in rats by the tail-cuff method, allowing readings when pulse/flow disappears during cuff inflation and reappears during deflation, separated by a compression interval. Although cuff deflation is habitually used to estimate SBP, we found cuff deflation-cuff inflation pressure to be usually negative, indicating that cuff deflation pressure < cuff inflation pressure. METHODS: SBP was measured in 226 male Wistar and SHR utilizing compression intervals of different durations, and also pharmacological interventions intended to modulate the cuff deflation-cuff inflation cycle. Direct, simultaneous intravascular measurements were also performed in some animals. RESULTS AND DISCUSSION: With compression interval congruent with 15 s, cuff deflation-cuff inflation was--6 +/- 0.6 mmHg in 73 Wistar and--6 +/- 1.4 mmHg in 51 SHR. Lengthening compression interval up to 4 min increased cuff deflation-cuff inflation pressure significantly to--27 +/- 3 mmHg in Wistar and to - 31 +/- 5 mmHg in SHR, suggesting accumulation of a vasodilating mediator. This increase of cuff deflation-cuff inflation pressure was prevented by papaverine (totally in Wistar, partially in SHR), indicating its dependence on vasodilatory capacity. Adrenergic blockade decreased cuff deflation-cuff inflation pressure to--13 +/- 5 mmHg (P < 0.05) in SHR, but had no effect in Wistar rats. Injection of L-NAME decreased cuff deflation-cuff inflation pressure to--5 +/- 2 mmHg (P < 0.05) in Wistar rats but was ineffective in SHR. Simultaneous measurements by tail-cuff method and carotid cannulation revealed that the cuff inflation most accurately estimated the intravascular SBP. CONCLUSIONS: 1) Cuff inflation measurements should be considered representative of SBP, as cuff deflation can underestimate SBP depending on compression interval duration, 2) nitric oxide accumulation due to flow deprivation is the main cause of SBP underestimation by cuff deflation in Wistar, and 3) in SHR, nitric oxide effects were minimal, and sympathetic activation plus physical factors seemed to predominate in the determining the outcome of measurements.

Both alpha1 and alpha2-adrenoceptors mediate the cardiovascular responses to noradrenaline microinjected into the bed nucleus of the stria terminal of rats.

BACKGROUND AND PURPOSE: We have previously shown that noradrenaline microinjected into the bed nucleus of stria terminalis (BST) elicited pressor and bradycardiac responses in unanaesthetized rats. In the present study, we investigated the subtype of adrenoceptors that mediates the cardiovascular response to noradrenaline microinjection into the BST. EXPERIMENTAL APPROACH: Cardiovascular responses following noradrenaline microinjection into the BST of male Wistar rats were studied before and after BST pretreatment with different doses of the selective alpha(1)-adrenoceptor antagonist WB4101, the alpha(2)-adrenoceptor antagonist RX821002, the combination of WB4101 and RX821002, the non-selective beta-adrenoceptor antagonist propranolol, the selective beta(1)-adrenoceptor antagonist CGP20712 or the selective beta(2)-adrenoceptor antagonist ICI118,551. KEY RESULTS: Noradrenaline microinjected into the BST of unanaesthetized rats caused pressor and bradycardiac responses. Pretreatment of the BST with different doses of either WB4101 or RX821002 only partially reduced the response to noradrenaline. However, the response to noradrenaline was blocked when WB4101 and RX821002 were combined. Pretreatment with this combination also shifted the resulting dose-effect curve to the left, clearly showing a potentiating effect of this antagonist combination. Pretreatment with different doses of either propranolol or CGP20712 increased the cardiovascular responses to noradrenaline microinjected into the BST. Pretreatment with ICI118,551 did not affect cardiovascular responses to noradrenaline. CONCLUSION AND IMPLICATIONS: The present results indicate that alpha(1) and alpha(2)-adrenoceptors mediate the cardiovascular responses to noradrenaline microinjected into the BST. In addition, they point to an inhibitory role played by the activation of local beta(1)-adrenoceptors in the cardiovascular response to noradrenaline microinjected into the BST.

Reversible anesthesia in wild marine otters (Lontra felina) using ketamine and medetomidine.

Nine marine otters (Lontra felina) were anesthetized 15 times with a combination of ketamine (5.3 +/- 0.9 [range: 4.5-8.0] mg/kg) and medetomidine (53 - 9 [range: 45-80] microg/kg) i.m. by hand syringe for the placement of radiotransmitters. Times to initial effect and induction period ranged from 1.1 to 5.0 min and 1.8 to 5.4 min, respectively. Minor complications did occur, including mild hypothermia in six otters and severe hypoxemia in one otter. After 34 and 63 min, anesthesia was antagonized with atipamezole (226 +/- 29 [range: 179-265] microg/kg) and all otters recovered within 3.3-26.8 min.

Dexmedetomidine prolongs spinal anaesthesia induced by levobupivacaine 0.5% in guinea-pigs.

Alpha-2 adrenoceptor agonists have been used in association with local anaesthetic to increase the duration of spinal anaesthesia. Intrathecal administration of clonidine prolonged motor blockade induced by local anaesthetic. Since the affinity of dexmedetomidine (DEX) to alpha-2 adrenoceptors is eight-times greater than clonidine, it is expected that DEX could be advantageous in clinical anaesthesia. We investigated the duration of motor nerve block induced by spinal injection of 0.5% levobupivacaine (LVB) associated with intrathecal or intraperitoneal administration of DEX. Seventy-two guinea-pigs were randomly divided in 12 groups, which were all treated with intrathecal injection of 50 microL of LVB. DEX was injected intrathecally with LVB in 6 groups or injected intraperitoneally after LVB in another 6 groups. Intrathecal DEX (0.1, 0.2 and 0.4 microg) increased the LVB-induced motor anaesthesia from 48 (41-66) min to 84.5 (52-91) min (P < 0.05), 101.5 (83-115) min (P < 0.05) and 105 (97-114) min (P < 0.05), respectively. Similarly, intraperitoneal DEX (20 and 40 microg kg(-1)) increased the motor blockade from 48.5 (33-59) min to 88 (71-114) min (P < 0.05) and 114.5 (103-156) min (P < 0.05), respectively. Pre-treatment with yohimbine reduced the duration of motor block from 101.5 (83-115) to 76.5 (68-86) min (P < 0.05) or from 114.5 (103-156) to 90 (83-93) min (P < 0.05) when DEX was administered by the intrathecal or intraperitoneal routes. Motor block induced by spinal injection of LVB was prolonged by intrathecal and systemic administration of DEX, which was partially dependent on activation of alpha-2 adrenoceptors.