Crotty T P
Anatomy Department, University College, Cork, Ireland.
Med Hypotheses. 1989 Apr;28(4):233-43. doi: 10.1016/0306-9877(89)90077-7.
Experiments have shown that noradrenaline can dilate the lateral saphenous vein of the dog when that vein has been constricted by noradrenaline, at the same concentration, in the first place. This dilator action of noradrenaline occurs when the drug stimulates the constricted vein through its outer surface after it is released from the vein's vasa vasorum network. There is evidence suggesting that this effect is not unique to noradrenaline and that the effect of any agonist stimulating a blood vessel through its lumenal surface may be reversed following its release from vasa vasorum. This phenomenon may be important in the context of the known relationship there is between the severity of the symptoms of atherosclerosis and the degree to which vasa vasorum proliferate de novo in the adventitia of blood vessels affected by that disease. It is suggested that in atherosclerosis endogenous vasodilators have their actions reversed by release from these pathological vasa. This would result in the vasodilators of exercise having a constrictor action on the coronary vessels and becoming the immediate cause of angina. If vasodilators do indeed cause angina then the use of beta-blockade in this condition becomes a rational rather than an empirical method of treatment. An hypothesis is advanced to explain the phenomenon of drug action reversal.
实验表明，当犬的隐外侧静脉首先被去甲肾上腺素以相同浓度收缩后，去甲肾上腺素能使其扩张。当药物从静脉的血管滋养管网释放后，通过其外表面刺激已收缩的静脉时，就会出现去甲肾上腺素的这种扩张作用。有证据表明，这种效应并非去甲肾上腺素所特有，任何通过血管腔表面刺激血管的激动剂在从血管滋养管释放后，其效应可能会逆转。鉴于动脉粥样硬化症状的严重程度与该疾病所累及血管外膜中新生血管滋养管的增生程度之间已知的关系，这一现象可能具有重要意义。有人提出，在动脉粥样硬化中，内源性血管舒张剂的作用会因从这些病理性血管滋养管释放而逆转。这将导致运动时的血管舒张剂对冠状动脉产生收缩作用，并成为心绞痛的直接原因。如果血管舒张剂确实会引发心绞痛，那么在这种情况下使用β受体阻滞剂就成为一种合理而非经验性的治疗方法。本文提出了一个假说以解释药物作用逆转的现象。
