血管紧张素II与Bay K 8644对家兔离体血管中通过接头后α1和α2肾上腺素能受体介导的去甲肾上腺素反应影响的比较
A comparison of the effects of angiotensin II and Bay K 8644 on responses to noradrenaline mediated via postjunctional alpha 1-and alpha 2-adrenoceptors in rabbit isolated blood vessels.
The effects of angiotensin II (AII) and Bay K 8644 on responses to noradrenaline (NA) mediated via postjunctional alpha 1- and/or alpha 2-adrenoceptors have been compared in three isolated venous preparations from the rabbit, the lateral saphenous vein, the left renal vein and the ear vein. 2. A similar action of AII and Bay K 8644 was observed only in the lateral saphenous vein; each potentiated responses to NA after isolation of a homogeneous population of postjunctional alpha 2- adrenoceptors. However, even in this preparation the mechanism of action for these agents was not identical. The sensitivity of KCl-induced contraction to changes in extracellular calcium ions (reflecting activation of voltage-dependent Ca2+ channels) was enhanced by Bay K 8644 but reduced by AII. 3. All produced a selective facilitation of responses mediated via postjunctional alpha 2-adrenoceptors. In the lateral saphenous vein it reduced the effectiveness of prazosin and facilitated responses after isolation of alpha 2-adrenoceptors with phenoxybenzamine and rauwolscine. It directly enhanced responses to NA in the ear vein, where only alpha 2-adrenoceptors are involved. In contrast, AII did not influence responses mediated via postjunctional alpha 1-adrenoceptors in the left renal vein (even after the receptor reserve had been removed with phenoxybenzamine) nor the 'rauwolscine-resistant' component of responses to NA in the saphenous vein. 4. Bay K 8644 enhanced contractile responses to NA mediated both via alpha 2-adrenoceptors, in the lateral saphenous vein, and via alpha 1-adrenoceptors in the left renal vein. Thus, unlike angiotensin II, no preferential effect was apparent. 5. Bay K 8644 was inactive against responses to NA in the rabbit isolated ear vein. Since the sustained component of responses to NA in this preparation is dependent upon the influx of extracellular Ca2 , these observations suggest that the influx of Ca2+ stimulated by NA is mediated via receptor-operated (1,4-dihydropyridine-resistant) Ca2 + channels.
摘要
已在取自家兔的三种离体静脉制剂（即外侧隐静脉、左肾静脉和耳静脉）中比较了血管紧张素II（AII）和Bay K 8644对经由节后α1和/或α2肾上腺素能受体介导的去甲肾上腺素（NA）反应的影响。2. 仅在外侧隐静脉中观察到AII和Bay K 8644有类似作用；在分离出同质的节后α2肾上腺素能受体群体后，它们均增强了对NA的反应。然而，即使在该制剂中，这些药物的作用机制也不相同。Bay K 8644增强了氯化钾诱导的收缩对细胞外钙离子变化的敏感性（反映电压依赖性Ca2+通道的激活），而AII则降低了这种敏感性。3. 二者均对经由节后α2肾上腺素能受体介导的反应产生选择性促进作用。在外侧隐静脉中，它降低了哌唑嗪的效力，并在用苯氧苄胺和萝芙木碱分离出α2肾上腺素能受体后增强了反应。它直接增强了耳静脉中对NA的反应，耳静脉中仅涉及α2肾上腺素能受体。相比之下，AII对左肾静脉中经由节后α1肾上腺素能受体介导的反应（即使在用苯氧苄胺消除受体储备后）以及隐静脉中对NA反应的“萝芙木碱抵抗”成分均无影响。4. Bay K 8644增强了外侧隐静脉中经由α2肾上腺素能受体介导的以及左肾静脉中经由α1肾上腺素能受体介导的对NA的收缩反应。因此，与血管紧张素II不同，未表现出明显的优先效应。5. Bay K 8644对家兔离体耳静脉中对NA的反应无活性。由于该制剂中对NA反应的持续成分依赖于细胞外Ca2+的内流，这些观察结果表明，NA刺激的Ca2+内流是通过受体操纵的（对1,4 - 二氢吡啶不敏感的）Ca2+通道介导的。
