de Souza Bruno Palmieri, da Silva Edilson Dantas, Jurkiewicz Aron, Jurkiewicz Neide Hyppolito
Department of Pharmacology, Universidade Federal de São Paulo - UNIFESP, Rua 3 de Maio 100, 04044-020 São Paulo-SP, Brazil.
Department of Pharmacology, Universidade Federal de São Paulo - UNIFESP, Rua 3 de Maio 100, 04044-020 São Paulo-SP, Brazil.
Eur J Pharmacol. 2014 Sep 5;738:118-24. doi: 10.1016/j.ejphar.2014.05.035. Epub 2014 Jun 2.
The effects of acute treatment with sibutramine on the peripheral sympathetic neurotransmission in vas deferens of young rats were still not evaluated. Therefore, we carried out this study in order to verify the effects of acute sibutramine treatment on the neuronal- and exogenous agonist-induced contractions of the young rat vas deferens. Young 45-day-old male Wistar rats were pretreated with sibutramine 6 mg/kg and after 4h the vas deferens was used for experiment. The acute treatment with sibutramine was able to increase the potency (pD2) of noradrenaline and phenylephrine. Moreover, the efficacy (Emax) of noradrenaline was increased while the efficacy of serotonin and nicotine were decreased. The maximum effect induced by a single concentration of tyramine was diminished in the vas deferens from treated group. Moreover, the leftward shift of the noradrenaline curves promoted by uptake blockers (cocaine and corticosterone) and β-adrenoceptor antagonist (propranolol) was reduced in the vas deferens of treated group. The initial phasic and secondary tonic components of the neuronal-evoked contractions of vas deferens from treated group at the frequencies of 2 Hz were decreased. Moreover, only the initial phasic component at 5 Hz was diminished by the acute treatment with sibutramine. In conclusion, we showed that the acute treatment with sibutramine in young rats was able to affect the peripheral sympathetic nervous system by inhibition of noradrenaline uptake and reduction of the neuronal content of this neurotransmitter, leading to an enhancement of vas deferens sensitivity to noradrenaline.
西布曲明急性治疗对幼鼠输精管外周交感神经传递的影响尚未得到评估。因此,我们开展了本研究,以验证西布曲明急性治疗对幼鼠输精管神经元和外源性激动剂诱导收缩的影响。45日龄的雄性Wistar幼鼠用6mg/kg西布曲明进行预处理,4小时后将输精管用于实验。西布曲明急性治疗能够增加去甲肾上腺素和去氧肾上腺素的效能(pD2)。此外,去甲肾上腺素的最大效应(Emax)增加,而5-羟色胺和尼古丁的最大效应降低。在处理组的输精管中,单一浓度酪胺诱导的最大效应减弱。此外,在处理组的输精管中,摄取阻滞剂(可卡因和皮质酮)和β-肾上腺素能受体拮抗剂(普萘洛尔)促进的去甲肾上腺素曲线左移减少。处理组输精管在2Hz频率下神经元诱发收缩的初始相性成分和继发性紧张性成分均降低。此外,西布曲明急性治疗仅使5Hz时的初始相性成分减弱。总之,我们表明,幼鼠西布曲明急性治疗能够通过抑制去甲肾上腺素摄取和减少该神经递质的神经元含量来影响外周交感神经系统,导致输精管对去甲肾上腺素的敏感性增强。