Imhof P R, Rennwald D, Müller P, Howald H, Burkart F
Research Department, Ciba-Geigy Ltd., Basle, Switzerland.
Methods Find Exp Clin Pharmacol. 1989 Jun;11(6):409-14.
In a placebo-controlled, double-blind, cross-over study in seven healthy volunteers, continuous transdermal administration of nitroglycerin over 48 h by means of Nitroderm TTS 10 evoked counter-regulations that interfered with the nitrate effects. These counter-regulations comprised an increase in sympathico-adrenal activity, manifested in elevated plasma levels of adrenaline and noradrenaline, and an internal hemodilution, readily perceptible from the decrease in the hematocrit readings. As a result, several of the circulatory effects of nitroglycerin were no longer in evidence, or much weaker on the second day of the study. The effects concerned were the reduction of systolic and diastolic blood pressure, the increase in heart rate, the prolongation of PEPc, and shortening of LVETc, and the change in digital-pulse morphology (increase in the a/b quotient). On the other hand, the increase in venous distensibility and the decrease in hematocrit were unaltered throughout the observation period. The attenuation of the action of nitroglycerin noticeable 24 h after application of the patches is, therefore, not indicative of any loss of effect of the substance per se, but due to the circulatory counter-regulations, which were largely confined to the arterial side of the circulation and scarcely affected the venous system. One or two hours after removal of the patches, counter-regulations had practically ceased.
在一项针对7名健康志愿者的安慰剂对照、双盲、交叉研究中，通过硝糖灵贴剂（Nitroderm TTS 10）连续48小时经皮给予硝酸甘油引发了对抗调节，干扰了硝酸盐的作用。这些对抗调节包括交感 - 肾上腺活动增加，表现为血浆肾上腺素和去甲肾上腺素水平升高，以及体内血液稀释，这可从血细胞比容读数的降低中明显看出。结果，硝酸甘油的几种循环效应在研究的第二天不再明显或明显减弱。所涉及的效应包括收缩压和舒张压降低、心率增加、射血前期（PEPc）延长、左室射血时间（LVETc）缩短以及指脉形态改变（a/b商增加）。另一方面，静脉扩张性增加和血细胞比容降低在整个观察期内未改变。因此，贴片应用24小时后硝酸甘油作用的减弱并非表明该物质本身的任何效应丧失，而是由于循环对抗调节，这种调节主要局限于循环的动脉侧，几乎未影响静脉系统。贴片移除一两个小时后，对抗调节实际上已经停止。
