Both alpha(1)- and beta(1)-adrenoceptors in the bed nucleus of the stria terminalis are involved in the expression of conditioned contextual fear

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

Uso de dexmedetomidina em neurocirurgia

JUSTIFICATIVA E OBJETIVOS: Os fármacos alfa2-agonistas são a cada dia mais utilizados em Anestesiologia, seja como adjuvantes ou como agentes anestésicos únicos. Atualmente, o emprego da dexmedetomidina vem se popularizando devido à sua maior seletividade aos receptores alfa2 e, também, ao seu perfil farmacocinético. O objetivo desta revisão foi fazer uma análise do emprego da dexmedetomidina em neurocirurgia. CONTEÚDO: Além das considerações e revisão da literatura quanto ao emprego da dexmedetomidina especificamente em procedimentos neurocirúrgicos, foi realizada descrição dos efeitos do fármaco nos diversos sistemas do organismo. CONCLUSÕES: A dexmedetomidina tem perfil farmacocinético e farmacodinâmico que favorece seu emprego em diversos procedimentos neurocirúrgicos. A utilização clínica em procedimentos cirúrgicos com craniotomia para pinçamento de aneurisma e remoção de tumores é crescente. Além disso, seu uso em intervenções cirúrgicas funcionais é promissor.

Interaction between arginine vasopressin and angiotensin II receptors in the central regulation of sodium balance

We speculated that the influence of lateral preoptic area (LPO) in sodium balance, involves arginine(8)-vasopressin (AVP) and angiotensin (ANG II) on Na+ uptake in LPO. Therefore, the present study investigated the effects of central administration of specific AVP and ANG 11 antagonists (d(CH2)(5)-Tyr (Me)-AVP (AAVP) and [Adamanteanacetyl(1), 0-ET-D-Tyr(2), Val(4), Aminobutyryl(6), Arg(8.9)]-AVP (ATAVP) antagonists of V-1 and V-2 receptors of AVP. Also the effects of losartan and CGP42112A (selective ligands of the AT(1) and AT(2) angiotensin receptors, respectively), was investigated on Na+ uptake and renal fluid and electrolyte excretion. After an acclimatization period of 7 days, the animals were maintained under tribromoethanol (200 mg/kg body weight, intraperitonial) anesthesia and placed in a Kopf stereotaxic instrument. Stainless guide cannula was implanted into the LPO. AAVP and ATAVP injected into the LPO prior to AVP produced a reduction in the NaCl intake. Both the AT(1) and AT(2) ligands administered into the LPO elicited a decrease in the NaCl intake induced by AVP injected into the LPO. AVP injection into the LPO increased sodium renal excretion, but this was reduced by prior AAVP administration. The ATAVP produced a decreased in the natriuretic effect of AVP. The losartan injected into LPO previous to AVP decreased the sodium excretion and the CGP 421122A also decreased the natriuretic effect of AVP. The AVP produced an antidiuresis effect that was inhibited by prior administration into LPO of the ATAVP. The AAVP produced no change in the antidiuretic effect of AVP. These results suggest that LPO are implicated in sodium balance that is mediated by V-1, V-2, AT(2) and AT(2) receptors. (c) 2005 Elsevier B.V All rights reserved.

Moxonidine and rilmenidine injected into the medial septal area reduces the salivation induced by pilocarpine

We determined the effects of moxonidine and rilmenidine 20 mol (alpha(2)-adrenergic and imidazoline receptor agonists) injected into the medial septal area (MSA) on the pilocarpine-induced salivation, when injected intraperitoneally (i.p.), of male Holtzman rats weighing 250300 g, with stainless-steel cannula implanted into the MSA. The rats were anesthetized with zoletil 50 mg kg(-1) b.wt. (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle intramuscularly (IM), saliva was collected using pre-weighed small cotton balls inserted in the animal's mouth. The pre-treatment with moxonidine injected into the MSA reduced the salivation induced by pilocarpine (1 mg kg(-1)) injected i.p. (12 +/- 3 mg min(-1)) vs. control (99 +/- 9 mg min(-1)). The pre-treatment with rilmenidine 40 nmol also reduced the salivation induce by pilocarpine injected i.p. (20 +/- 5 mg min(-1)) vs. control (94 +/- 7 mg min(-1)). Idazoxan 40 nmol (imidazoline receptor antagonist) injected into the MSA previous to moxonidine and rilmenidine partially blocked the effect of moxonidine and totally blocked the rilmenidine effect in pilocarpine-induced salivation injected i.p. (60 +/- 8 and 95 +/- 10 mg min(-1), respectively). Yohimbine 40 nmol (alpha(2)-adrenergic receptor antagonist) injected into the MSA previously to moxonidine and rilmenidine partially blocked the moxonidine effect but produced no change on the rilmenidine effect on i.p. pilocarpine-induced salivation (70 +/- 6 and 24 +/- 6 mg min(-1), respectively). Injection of these alpha(2)-adrenergic and imidazoline agonists and antagonists agents i.p. produced no change on i.p. pilocarpine-induced salivation. These results show that central, but not peripheral, injection of alpha(2)-adrenergic and imidazoline agonists' agents inhibit pilocarpine-induced salivation. Idazoxan, an imidazoline receptor antagonist, totally inhibits the rilmenidine effect and partially inhibits the moxonidine effect on pilocarpine-induced salivation. Yohimbine produced no change on rilmenidine effect but partially inhibited the moxonidine effect. Both of these antagonists when injected into the MSA previous to pilocarpine i.p. potentiated the sialogogue effect of pilocarpine. The results suggest that alpha(2)-adrenergic/imidazoline receptor of the MSA when stimulated blocked pilocarpine-induced salivation in rats when injected intraperitonially These receptors of the medial septal area have an inhibitory mechanism on salivary secretion. (C) 2004 Elsevier B.V. All rights reserved.

Moxonidine reduces pilocarpine-induced salivation in rats

Cholinergic, agonists activate salivation and the alpha (2)-adrenergic and imidazoline receptor agonists induce opposite effects. In the present study, we investigated the effects of intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of moxonidine (an a-adrenergic and imidazoline receptor agonist) on the salivation induced by the cholinergic agonist pilocarpine. Male Holtzman rats wish stainless steel cannula implanted into the lateral ventricle (LV) were used. In rats anesthetized with tribromoethanol (200 mg kg(-1)), saliva was collected using pre-weighed small cotton balls inserted in the animal's mouth. The treatment with moxonidine (5, 10 and 20 nmol in 1 mul) injected,i.c.v. reduced the salivation induced by pilocarpine (1 mg kg(-1)) injected i.p. (48 +/- 5, 17 +/- 2 and 15 +/- 2 mg min(-1) vs. control, 73 +/- 7 mg min(-1)). The same doses of moxonidine injected i.c.v. also reduced the salivary secretion induced by pilocarpine (500 nmol in 1 mul). injected i.c.v. (44 +/- 1, 14 +/- 2 and 20 +/- 3 mg min(-1) vs. control, 51 +/- 2 mg min(-1)). Injection of moxonidine (20 nmol in 0.1 ml) i.p. produced no chance on i.p. pilocarpine-induced salivation (58 +/- 4 mg min(-1) vs. control, 50 +/- 4 mg min(-1)). The results show that central, but not peripheral, injection of moxonidine inhibit,. pilocarpine-induced salivation, suggesting that central mechanisms activated by alpha (2)-adrenergic/imidazoline agonists inhibit cholinergic-induced salivation in rats. (C) 2001 Elsevier B.V. B.V. All rights reserved.

Role of the alpha(1)- and alpha(2)-adrenoceptors of the paraventricular nucleus on the water and salt intake, renal excretion, and arterial pressure induced by angiotensin II injection into the medial septal area

In this study we investigated the influence of cu-adrenergic antagonists injections into the paraventricular nucleus (PVN) of the hypothalamus on the thirst and salt appetite, diuresis, natriuresis, and presser effects of angiotensin II (ANG II) stimulation of medial septal area (MSA). ANG II injection into the MSA induced water and sodium intake, diuresis, natriuresis, and presser responses. The previous injection of prazosin (an alpha (1)-adrenergic antagonist) into the PVN abolished, whereas previous administration of yohimbine (an alpha (2)-adrenergic antagonist) into the PVN increased the water and sodium intake, urinary, natriuretic, and presser responses induced by ANG ii injected into the MSA. Previous injection of a nonselective alpha -adrenergic antagonist, regitin, into the PVN blocked the urinary excretion, and reduced the water and sodium intake, sodium intake, and presser responses induced by ANG II injected into the MSA. The present results suggest that alpha -adrenergic pathways involving the PVN are important for the water and sodium excretion, urine and sodium excretion, and presser responses, induced by angiotensinergic activation of the MSA. (C) 2001 Elsevier B.V.

Exercício físico, receptores β-adrenérgicos e resposta vascular

O exercício aeróbio promove efeitos benéficos na prevenção e tratamento de doenças como hipertensão arterial, aterosclerose, insuficiência venosa e doença arterial periférica. Os receptores β-adrenérgicos estão presentes em várias células. No sistema cardiovascular, promovem inotropismo e cronotropismo positivo cardíaco e relaxamento vascular. Embora os efeitos do exercício tenham sido investigados em receptores cardíacos, estudos focados nos vasos são escassos e controversos. Esta revisão abordará os efeitos do exercício físico sobre os receptores β-adrenérgicos vasculares em modelos animais e humanos e os mecanismos celulares envolvidos na resposta relaxante. em geral, os estudos mostram resultantes conflitantes, onde observam diminuição, aumento ou nenhum efeito do exercício físico sobre a resposta relaxante. Assim, os efeitos do exercício na sensibilidade β-adrenérgica vascular merecem maior atenção, e os resultados mostram que a área de fisiopatologia vascular é um campo aberto para a descoberta de novos compostos e avanços na prática clínica.

Adrenoceptors of the medial septal area modulate water intake and renal excretory function induced by central administration of angiotensin II

We investigated the role of alpha-adrenergic antagonists and clonidine injected into the medial septal area (MSA) on water intake and the decrease in Na+, K+ and urine elicited by ANGII injection into the third ventricle (3rdV). Male Holtzman rats with stainless steel cannulas implanted into the 3rdV and MSA were used. ANGII (12 nmol/µl) increased water intake (12.5 ± 1.7 ml/120 min). Clonidine (20 nmol/µl) injected into the MSA reduced the ANGII-induced water intake (2.9 ± 0.5 ml/120 min). Pretreatment with 80 nmol/µl yohimbine or prazosin into the MSA also reduced the ANGII-induced water intake (3.0 ± 0.4 and 3.1 ± 0.2 ml/120 min, respectively). Yohimbine + prazosin + clonidine injected into the MSA abolished the ANGII-induced water intake (0.2 ± 0.1 and 0.2 ± 0.1 ml/120 min, respectively). ANGII reduced Na+ (23 ± 7 µEq/120 min), K+ (27 ± 3 µEq/120 min) and urine volume (4.3 ± 0.9 ml/120 min). Clonidine increased the parameters above. Clonidine injected into the MSA abolished the inhibitory effect of ANGII on urinary sodium. Yohimbine injected into the MSA also abolished the inhibitory effects of ANGII. Yohimbine + clonidine attenuated the inhibitory effects of ANGII. Prazosin injected into the MSA did not cause changes in ANGII responses. Prazosin + clonidine attenuated the inhibitory effects of ANGII. The results showed that MSA injections of alpha1- and alpha2-antagonists decreased ANGII-induced water intake, and abolished the Na+, K+ and urine decrease induced by ANGII into the 3rdV. These findings suggest the involvement of septal alpha1- and alpha2-adrenergic receptors in water intake and electrolyte and urine excretion induced by central ANGII.

Injeção epidural preventiva de xilazina ou amitraz em eqüinos: efeitos clínicos e comportamentais

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

LESIONS OF THE LATERAL HYPOTHALAMUS IMPAIR THE PRESSOR-RESPONSE TO CLONIDINE INJECTED INTO THE MEDIAL SEPTAL AREA OF CONSCIOUS RATS

The central injection of clonidine (an alpha-2-adrenoceptor agonist) in conscious normotensive rats produces hypertensive responses and bradycardia. The present study was performed to investigate the effect of electrolytic lesions of the lateral hypothalamus (LH) on the pressor and bradycardic responses induced by clonidine injected into the medial septal area (MSA) in conscious and unrestrained rats. Male Holtzman rats weighing 250-300 g were used. Mean arterial pressure and heart rate were recorded in sham- or bilateral LH-lesioned rats with a cerebral stainless steel cannula implanted into the MSA. The injection of clonidine (40 nmol/mu-l) into the MSA of sham rats (N = 8) produced a pressor response (36 +/- 7 mmHg, P<0.05) and bradycardia (-70 +/- 13 bpm, P<0.05) compared to saline. Fourteen days after LH-lesion (N = 9) the pressor response was reduced (9 +/- 10 mmHg, P<0.05) but no change was observed in the bradycardia (-107 +/- 24 bpm). These results show that LH is an important area involved in the pressor response to clonidine injected into the MSA of rats.

Receptor-mediated effects of clonidine on need-induced 3% NaCl and water intake

Clonidine combined with adrenergic antagonists were injected in the medial septal area in order to characterize the type of receptors involved with its inhibitory effect on 3% NaCl and water intake of sodium-depleted (furosemide + 24 h of removal of ambient sodium) and 30-h water-deprived rats, respectively. The inhibitory effect of clonidine (20 nmol) on need-induced water intake was reduced 50% by an 80-nmol dose of either idazoxan, yohimbine or prazosin. The inhibitory effect of clonidine (30 nmol) on need-induced 3% NaCl intake was completely antagonized by idazoxan (80, 160 nmol), not altered by yohimbine (40-160 nmol), and partially potentiated (40 nmol) or inhibited (160 nmol) by prazosin. Propranolol did not alter the effects of clonidine on either water (80 nmol) or 3% NaCl (40-160 nmol) intake. The results suggest that the inhibitory effects of clonidine on 3% NaCl and water intake are mediated by different types of alpha2-adrenergic receptors. Copyright (C) 1997 Elsevier B.V.

Recent developments for smoking cessation and treatment of nicotine dependence

Nicotine is an addictive drug like heroin, amphetamine or cocaine. Addiction to tobacco leads to significant failure rates in programmes for smoking cessation. The alpha(4)beta(2) and alpha(7) nicotinic acetylcholine receptors (nAChRs) and CB1 cannabinoid receptors play an important role in nicotine addiction.

Ventromedial hypothalamus lesions increase the dipsogenic responses and reduce the pressor responses to median preoptic area activation

In this study, we investigated the participation of adrenergic receptors of the median preoptic area (MnPO) and the participation of ventromedial hypothalamus (VMH) in angiotensin II- (ANG II)-induced water intake and presser responses. Male rats with sham or electrolytic VMH lesions and a stainless steel cannula implanted into the MnPO were used. Noradrenaline, clonidine (an alpha(2)-adrenergic receptor agonist), or phenylephrine (an alpha(1)-adrenergic receptor agonist) injected into the MnPO of sham-lesioned rats reduced water ingestion induced by ANG II injected into the same area. In VMH-lesioned rats ANG II-induced water intake increased with a previous injection of noradrenaline, phenylephrine, or isoproterenol. The presser response induced by ANG II injected into the MnPO was reduced in VMH-lesioned rats, whereas the presser response induced by clonidine was abolished. Previous treatment with noradrenaline and phenylephrine into the MnPO of sham-lesioned rats produced a presser response, and a hypotensive response was obtained with the previous administration of noradrenaline, phenylephrine or isoproterenol into the MnPO of VMH-lesioned rats. These results show that VMH is essential for the dipsogenic and presser responses induced by adrenergic and angiotensinergic activation of the MnPO in rats. (C) 1997 Elsevier B.V.

Noradrenergic response in vas deferens from rats submitted to acute and repeated stress

1. This work investigated the effects of androgens on the norepinephrine sensitivity of vasa deferentia from rats submitted to acute or repeated stress, as well as the participation of alpha(1)-adrenoceptors in the response of intact and bisected vasa deferentia from adult normal rats submitted to acute or repeated stress.2. The acute stress produced subsensitivity to norepinephrine only in intact vasa deferentia from adult normal rats, which was prevented by lack of androgens, suggesting that the sensitivity may be dependent on the physiological level of androgen,3. No change was observed in intact vas deferens sensitivity to norepinephrine in repeated stress, suggesting the occurrence of adaptation to elevated norepinephrine levels or a mild decrease in androgen levers or both.4. The changes in sensitivity observed in acute and repeated stress may also be due to alterations in alpha(1)-adrenergic receptors that are located in the prostatic portion of the vas deferens. (C) 1998 Elsevier B.V.

Factors which affect the catalytic activity of iron(III) meso tetrakis(2,6-dichlorophenyl)porphyrin chloride in homogeneous system

An optimization study of the reaction conditions of Fe(TDCPP)Cl when it is used as catalyst in the hydroxylation of cyclohexane by iodosylbenzene (PhIO) has been carried out, It was found that Fe(TDCPP)Cl follows the classical PhIO mechanism described for Fe(TPP)Cl, which involves the monomeric active species Fe-IV(O)P-+. (I). In the optimized condition ([Fe(TDCPP) = 3.0 X 10(-4) mol l(-1) in 1,2-dichloroethane (DCE); ultrasound stirring at 0 degrees C; PhIO/FeP molar ratio = 100), this FeP led to a yield of cyclohexanol (C-ol) of 96% and a turnover number of 96, Therefore, Fe(TDCPP)Cl may be considered a good biomimetic model and a very stable, resistant and selective catalyst, which yields C-ol as the sole product. DCE showed to be a better solvent than dichloromethane (DCM), 1 DCE:1 MeOH mixture or acetonitrile (ACN). Since the Fe-IV(O)P-+. is capable of abstracting hydrogen atom from DCM, MeOH or ACN, the solvent competes with the substrate. Presence of O-2 lowers the yield of C-ol, as it can further oxidize this alcohol to carboxylic acid in the presence of radicals, Presence of H2O also causes a decrease in the yield, since it converts the active species I into Fe-IV(OH)P, which cannot oxidize cyclohexane. Addition of excess imidazole or OH- to the system results in a decrease in the yield of C-ol, due to the formation of the hexacoordinated complexes Fe(TDCPP)Im(2)(+) (low-spin, beta(2) = 2.5 X 10(8) mol(-2) l(2)) and Fe(TDCPP)(OH)(2)(-) (high-spin, beta(2) = 6.3 X 10(7) mol(-2) l(2)), the formation of both Fe(TDCPP)Im(2)(+) and Fe(TDCPP)(OH)(2)(-) complexes were confirmed by EPR studies. The catalytic activities of Fe(TDCPP)C and Fe(TFPP)Cl were compared, the unusually high yields of C-ol with Fe(TFPP)Cl obtained when ultrasound, DCM and O-2 atmosphere were used, suggest that a parallel mechanism involving the mu-oxo dimer form, O-2 and radicals may also be occurring with this FeP, besides the PhIO mechanism.