Hudlicka O, Reit E
Br J Pharmacol. 1977 Dec;61(4):587-95. doi: 10.1111/j.1476-5381.1977.tb07552.x.
1 The effects of several vasoactive substances have been studied on blood flow and acetylochline-induced contraction of the vascularly isolated gastrocnemius of the cat. All substances, including acetylcholine, were administered intra-arterially to the muscle. Blood flow and contractile tension were monitored simultaneously.2 All substances which increased blood flow, enhanced the contractile responses to acetylcholine; angiotensin, which decreased blood flow, attenuated them.3 Histamine was typical of the vasodilators in doses up to 1 mug (9 nmol), but in a dose tenfold higher it produced only a small and transient increase in blood flow and little or no enhancement of the acetylcholine-induced contractions. These paradoxical effects were brought about by that portion of the high dose of histamine which re-entered the cat's systemic circulation.4 The order of potency of the vasodilators was the same for their potentiating effect on the acetylcholine-induced contractile responses as for their enhancing effect on muscle blood flow: bradykinin >histamine>>papaverine>>NaH(2)PO(4) >KCl. Median effective doses (ED(50)S) determined only for bradykinin, histamine and papaverine were, respectively, 20.5, 49.8, and 3,352 pmol as potentiators, and 13.4, 199.8 and 85,000 pmol as vasodilators.5 In general, the effect of a given vasoactive substance on the contractile response to acetylcholine was dose-dependent and correlated well with its effect on muscle blood flow at the moment the acetylcholine was injected. Two important exceptions were, firstly, that the highest dose of papaverine was only moderately effective as a potentiator even though highly effective as an increaser of muscle blood flow; and, secondly, that histamine produced its greatest potentiating effect 10 s after it was injected, at which time its effect on muscle blood flow was quite small.6 It is suggested that these exceptions and, indeed, the much greater potentiating effectiveness of histamine and bradykinin versus papaverine may be due to the ability of histamine and bradykinin to increase the permeability of the muscle's capillaries as well as increasing blood flow through them, thus facilitating much better than mere vasodilators the access of bloodborne acetylcholine to its receptors on the muscle fibres.
研究了几种血管活性物质对猫离体腓肠肌血流量以及乙酰胆碱诱导的血管收缩的影响。所有物质，包括乙酰胆碱，均通过动脉内给药至肌肉。同时监测血流量和收缩张力。
所有增加血流量的物质均增强了对乙酰胆碱的收缩反应；而减少血流量的血管紧张素则减弱了这种反应。
组胺在剂量高达1微克（9纳摩尔）时是典型的血管舒张剂，但在剂量高10倍时，它仅使血流量产生微小且短暂的增加，对乙酰胆碱诱导的收缩几乎没有增强作用。这些矛盾的效应是由高剂量组胺中重新进入猫体循环的那部分引起的。
血管舒张剂对乙酰胆碱诱导的收缩反应的增强作用顺序与其对肌肉血流量的增强作用顺序相同：缓激肽＞组胺＞＞罂粟碱＞NaH₂PO₄＞KCl。仅针对缓激肽、组胺和罂粟碱测定的半数有效剂量（ED₅₀），作为增强剂时分别为20.5、49.8和3352皮摩尔，作为血管舒张剂时分别为13.4、199.8和85000皮摩尔。
一般来说，给定血管活性物质对乙酰胆碱收缩反应的影响呈剂量依赖性，并且在注射乙酰胆碱时与其对肌肉血流量的影响密切相关。有两个重要例外，首先，即使罂粟碱作为肌肉血流量增加剂非常有效，其最高剂量作为增强剂时效果也只是中等；其次，组胺在注射后10秒产生最大的增强作用，此时其对肌肉血流量的影响相当小。
有人认为，这些例外情况，以及事实上组胺和缓激肽相对于罂粟碱具有更强的增强作用，可能是由于组胺和缓激肽能够增加肌肉毛细血管的通透性以及增加通过它们的血流量，从而比单纯的血管舒张剂更有利于血液中乙酰胆碱与肌肉纤维上的受体结合。
