Recio Paz, Orensanz Luis M, Martínez María Pilar, Navarro-Dorado Jorge, Bustamante Salvador, García-Sacristán Albino, Prieto Dolores, Hernández Medardo
Departamento de Fisiología (Fisiología Animal), Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Naunyn Schmiedebergs Arch Pharmacol. 2008 Feb;376(6):397-406. doi: 10.1007/s00210-007-0227-x. Epub 2008 Jan 3.
The current study investigated the distribution of adrenergic nerves and the action induced by noradrenaline (NA) in pig prostatic small arteries. Noradrenergic innervation was visualized using an antibody against dopamine-beta-hydroxylase (DBH), and the NA effect was studied in small arterial rings mounted in microvascular myographs for isometric force recordings. DBH-immunoreactive nerve fibers were located at the adventitia and the adventitia-media border of the vascular wall. Electrical field stimulation (EFS, 1-32 Hz) evoked frequency-dependent contractions that were reduced by guanethidine and prazosin (adrenergic neurotransmission and alpha1-adrenoceptors blockers, respectively) and by the alpha2-adrenoceptor agonist UK 14,304. The alpha2-adrenoceptor antagonist rauwolscine reversed the UK 14,304-produced inhibition. NA produced endothelium-independent contractions that were antagonized with low estimated affinities and Schild slopes different from unity by prazosin and the alpha1A-adrenoceptor antagonist N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha-alpha-dimethyl-1H-indole-3-ethanamine (RS 17053). The alpha1A-adrenoceptor antagonist 5-methyl-3-[3-[4-[2-(2,2,2,-trifluoroethoxy) phenyl]-1-piperazinyl]propyl]-2,4-(1H)-pyrimidinedione (RS 100329), which also displays high affinity for alpha1L-adrenoceptors, and the alpha1L-adrenoceptor antagonist tamsulosin, which also has high affinity for alpha1A- and alpha1D-adrenoceptors, induced rightward shifts with high affinity of the contraction-response curve to NA. The alpha1D-adrenoceptor antagonist 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]8-azaspiro[4,5]decane-7,9-dione dihydrochloride (BMY 7378) failed to modify the NA contractions that were inhibited by extracellular Ca2+ removal and by voltage-activated (L-type) Ca2+ channel blockade. These data suggest that pig prostatic resistance arteries have a rich noradrenergic innervation; and NA, whose release is modulated by prejunctional alpha2-adrenoceptors, evokes contraction mainly through activation of muscle alpha1L-adrenoceptors coupled to extracellular Ca2+ entry via voltage (L-type)- and non-voltage-activated Ca2+ channels.
本研究调查了猪前列腺小动脉中肾上腺素能神经的分布以及去甲肾上腺素（NA）诱导的作用。使用抗多巴胺-β-羟化酶（DBH）的抗体来显示去甲肾上腺素能神经支配，并在安装于微血管肌动描记器中的小动脉环上研究NA的作用，以进行等长力记录。DBH免疫反应性神经纤维位于血管壁的外膜和外膜-中膜交界处。电场刺激（EFS，1 - 32 Hz）引起频率依赖性收缩，这种收缩被胍乙啶和哌唑嗪（分别为肾上腺素能神经传递阻滞剂和α1肾上腺素能受体阻滞剂）以及α2肾上腺素能受体激动剂UK 14,304所减弱。α2肾上腺素能受体拮抗剂萝芙辛逆转了UK 14,304产生的抑制作用。NA产生非内皮依赖性收缩，哌唑嗪和α1A肾上腺素能受体拮抗剂N-[2-(2-环丙基甲氧基苯氧基)乙基]-5-氯-α-α-二甲基-1H-吲哚-3-乙胺（RS 17053）以低估计亲和力和不同于1的Schild斜率对其进行拮抗。α1A肾上腺素能受体拮抗剂5-甲基-3-[3-[4-[2-(2,2,2-三氟乙氧基)苯基]-1-哌嗪基]丙基]-2,4-(1H)-嘧啶二酮（RS 100329），其对α1L肾上腺素能受体也显示出高亲和力，以及α1L肾上腺素能受体拮抗剂坦索罗辛，其对α1A和α1D肾上腺素能受体也具有高亲和力，使对NA的收缩反应曲线以高亲和力向右移位。α1D肾上腺素能受体拮抗剂8-[2-[4-(2-甲氧基苯基)-1-哌嗪基]乙基]-8-氮杂螺[4,5]癸烷-7,9-二酮二盐酸盐（BMY 7378）未能改变被细胞外Ca2+去除和电压激活（L型）Ca2+通道阻滞剂抑制的NA收缩。这些数据表明猪前列腺阻力动脉具有丰富的去甲肾上腺素能神经支配；并且NA的释放受突触前α2肾上腺素能受体调节，其主要通过激活与细胞外Ca2+经电压（L型）和非电压激活Ca2+通道内流偶联的肌肉α1L肾上腺素能受体来引发收缩。
