在大鼠胸主动脉环形和纵向制剂中,前列环素可能参与对“体外”去甲肾上腺素的不同强直反应

M. Chaud, A.M. Franchi, M.A.F. Gimeno, A.L. Gimeno
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引用次数: 1

摘要

鉴于已有的报告显示,“体外”去甲肾上腺素(NE)收缩环状大鼠主动脉准备,而在器官槽内,它使纵向排列的动脉条松弛,因此决定探索可能的原因,以解释同一医生对同一组织的不同作用。从大鼠胸主动脉获得的分离环(圆形制剂)对NE浓度的增加有剂量依赖性的滋补增强反应,不受吲哚美辛存在的显著影响(10−6M);而用酚妥拉明(10−6M)、育亨宾(10−7M)或哌唑嗪(10−8M)预孵育后,NE的正性肌力剂量-反应曲线的右点明显偏移。相反,纵向安装的大鼠主动脉瓣制剂对NE浓度的增加有剂量依赖性的松弛反应,这种效应不会被β -肾上腺素受体阻滞剂,即心得安(10−6M)的存在所改变。然而,当肾上腺素受体阻滞剂,如酚妥拉明(10−6M)、柔亨宾(10−7M)或吡唑嗪(10−8M)存在时,NE的负性肌力剂量-反应曲线向右移动,而在吲哚美辛(10−6M)或丙氨酰环丙胺(2.5×10−4M)存在时,NE诱导的松弛要么被消除,要么显著向右移动。在另一系列实验中,研究了大鼠主动脉与(1-14C)-花生四烯酸孵育1小时后,标记的6-酮前列腺素F1 α(前列环素最重要的非酶代谢产物)的生成,发现NE (3 × 10−6M)显著增强了标记的6-酮前列腺素F1 α的生成。目前的证据表明,NE作用于α -肾上腺素受体,诱导纵向和切碎动脉制剂,而不是主动脉环,一种抑制性松弛因子,可能是由内皮细胞产生的。这个因素可能是前列环,因为激动剂的松弛作用受到两种已知的PGI2形成拮抗剂吲哚美辛和环丙环胺的负面影响。在血管环(环形动脉制剂)中,NE的强张性刺激作用(不受吲哚美辛预培养的影响)是激动剂唯一明显的肌力作用,这可能是因为对组织的广泛处理以及随后在浴液中安装动脉制剂以进行收缩记录的锚定过程,可能会产生去内皮化。此外,有观点认为,在完整性保存较好的NE制剂中,主动脉前列环素合成明显增加,可能代表了一种局部调节机制,控制了交感神经激活的血管反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Possible prostacyclin involvement on disparate tonic responses to “in vitro” norepinephrine in circular and in longitudinal preparations from rat thoracic aorta

In view of existing reports documenting that “in vitro” norepinephrine (NE) contracts ring-shaped rat aortic preparations, whereas it relaxes arterial strips mounted in longitudinal fashion within an organ bath: it was decided to explore possible reasons which may account for such disparate: actions of the same ogonist on the same tissue. Isolated rings (circular preparations) obtained from rat thoracic aortae responded to increasing concentrations of NE with dose-dependent tonic enhancement, not significantly affected by the presence of indomethacin (10−6M); whereas, preincubation with phentolamine (10−6M), yohimbine (10−7M)or prazosin (10−8M), shifted significantly to the right points of the positive inotropic dose-response curve for NE. On the contrary longitudinally mounted preparations of rat aortic stips, reacted to increasing concentrations of NE with dose-dependent relaxation, an effect not modified by the presence of a beta-adrenoreceptor blocker, namely propranolol (10−6M). However, in presence of alpha-adrenoreceptor blockers, such as phentolamine (10−6M), yohimbine (10−7M) or prazosin (10−8M), the negative inotropic dose-response curve for NE was shifted to the right whereas in the pres nce of indomethacin (10−6M) or of tranylcypromine (2.5×10−4M), the NE-induced relaxation was either abolished or significantly displaced to the right, respectively. In another series of experiments the generation of labelled 6-keto-prostaglandin F1 α(the most important non-enzymatic metabolite of prostacyclin) by chopped rat aortae incubated for one hour with (1-14C)-arachidonic acid, was explored and found to be significantly enhanced by the delivery of NE (3 × 1O−6M). The present evidence suggests that NE acting on alpha-adrenoreceptors, induces in longitudinal and in chopped arterial preparations, but not in aortic rings, an inhibitory relaxing factor, presumably produced by the endothelium. This factor is probably prostacyclifor the relaxing effects of the agonist were negatively influence by indomethacin and by tranycypromine, two known antagonists of PGI2 formation. In vascular rings (circular arterial preparations) the tonic stimulatory action of NE (not affected by preincubation with indomethacin) was the only evident inotropic effect of the agonist presumably because the extensive handling of the tissue as well as the anchoring procedure followed to mount arterial preparations within the bath for contractile recordings, may produce de-endothelization. Moreover, the notion is advanced that the apparently greater aortic prostacyclin synthesis after NE in preparations with better preserved integrity may represent a local modulating mechanism, controlling vascular responses to sympathetic activation.

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