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苯氧苄胺增强对催产素和血管加压素升压反应的部位及机制:体内和离体主动脉条研究

The site and the mechanism of phenoxy-benzamine potentiation of the pressor response to oxytocin and vasopressin: in vivo and isolated aortic strips studies.

作者信息

Erker E F, Chan W Y

出版信息

J Pharmacol Exp Ther. 1977 Aug;202(2):287-93.

PMID:886467
Abstract

In intact rats, alpha adrenergic receptor blocking agents, phenoxybenzamine (PBZ) and phentolamine potentiated the pressor response to oxytocin and vasopressin (VP). In the presence of PBZ or phentolamine blockade, the dose-response curves of oxytocin and VP were shifted to the left, resulting in an apparent doubling of the pressor potency of the neurohypophysial peptides. The beta adrenergic blocking agent, propranolol had no significant effect on the pressor response to oxytocin or VP. Combined PBZ and propranolol blockade did not alter the potentiating activity of PBZ. The PBZ-potentiating effect seems to be specific to the neurohypophysial peptides, since the pressor response to angiotensin was not potentiated by PBZ. The potentiating effect of PBZ on VP could be demonstrated in isolated rat aortic strips. This clearly indicated that the site of action of PBZ is directly on the vascular smooth muscle. However, in aortic strips, the effect of PBZ was seen only if norepinephrine (NE) was also added to the bathing medium. NE alone had no significant effect on the contractile response to VP. The requirement of both PBZ and NE for the potentiating effect suggests that an interaction between these two agents is involved in the PBZ potentiation of VP response. The possibility that NE and not PBZ is the direct agent causing the potentiation of VP response is discussed.

摘要

在完整的大鼠中,α肾上腺素能受体阻断剂酚苄明(PBZ)和酚妥拉明可增强对催产素和血管加压素(VP)的升压反应。在PBZ或酚妥拉明阻断的情况下,催产素和VP的剂量反应曲线向左移动,导致神经垂体肽的升压效力明显加倍。β肾上腺素能阻断剂普萘洛尔对催产素或VP的升压反应无显著影响。联合使用PBZ和普萘洛尔阻断并不改变PBZ的增强活性。PBZ的增强作用似乎对神经垂体肽具有特异性,因为PBZ并未增强对血管紧张素的升压反应。PBZ对VP的增强作用可在离体大鼠主动脉条中得到证实。这清楚地表明PBZ的作用位点直接在血管平滑肌上。然而,在主动脉条中,只有在浴液中也加入去甲肾上腺素(NE)时才能观察到PBZ的作用。单独使用NE对VP的收缩反应无显著影响。PBZ和NE对增强作用的需求表明这两种药物之间的相互作用参与了PBZ对VP反应的增强。文中讨论了是NE而非PBZ直接导致VP反应增强的可能性。

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Br J Pharmacol. 1985 Sep;86(1):79-87. doi: 10.1111/j.1476-5381.1985.tb09437.x.