Sakai K, Saito K
Central Research Laboratories, Chugai Pharmaceutical, Tokyo, Japan.
Eur J Pharmacol. 1998 Jul 10;352(2-3):229-36. doi: 10.1016/s0014-2999(98)00357-4.
We hypothesized that the effect of nicorandil may be enhanced by interaction with naturally occurring vasodilators. To clarify this hypothesis, the effects of low-dose nicorandil alone and in combination with low doses of vasoactive intestinal polypeptide (VIP) or calcitonin gene-related peptide (CGRP) on adenosine-induced vasodepression were studied in rats. Intravenous (i.v.) bolus injections of adenosine (3-100 microg kg(-1)) elicited dose-dependent decreases in blood pressure, accompanied by slight decreases (except for 100 microg kg(-1)) in heart rate. Simultaneous i.v. infusion of either nicorandil (1 microg kg(-1) min(-1)) and VIP (0.003 microg kg(-1) min(-1)) or CGRP (0.1 ng kg(-1) min(-1)) significantly enhanced the adenosine-induced vasodepression, although each agent alone in the dose used had no effects on vasodepressor responses to adenosine. The potentiation of the effect of adenosine was not observed in the presence of 3,7-dimethyl-1-propargylxanthine (DMPX) (1 mg kg(-1), i.v.) or glibenclamide (20 mg kg(-1), i.v.). The present results suggest that low-dose nicorandil modifies the response to adenosine in interaction with low levels of endogenous neuropeptides such as VIP and CGRP, and that the reciprocal interaction is mediated partly through K(ATP) channel activation in vascular smooth muscle.
我们推测，尼可地尔与天然存在的血管舒张剂相互作用可能会增强其效果。为了验证这一推测，我们研究了低剂量尼可地尔单独使用以及与低剂量血管活性肠肽（VIP）或降钙素基因相关肽（CGRP）联合使用时，对大鼠腺苷诱导的血管减压作用的影响。静脉推注腺苷（3 - 100 μg kg⁻¹）可引起血压呈剂量依赖性下降，同时心率略有下降（100 μg kg⁻¹剂量除外）。同时静脉输注尼可地尔（1 μg kg⁻¹ min⁻¹）和VIP（0.003 μg kg⁻¹ min⁻¹）或CGRP（0.1 ng kg⁻¹ min⁻¹）可显著增强腺苷诱导的血管减压作用，尽管所用剂量的每种药物单独使用时对腺苷引起的血管减压反应均无影响。在存在3,7 - 二甲基 - 1 - 炔丙基黄嘌呤（DMPX）（1 mg kg⁻¹，静脉注射）或格列本脲（20 mg kg⁻¹，静脉注射）的情况下，未观察到腺苷作用的增强。目前的结果表明，低剂量尼可地尔与低水平的内源性神经肽如VIP和CGRP相互作用时可改变对腺苷的反应，并且这种相互作用部分是通过血管平滑肌中的K(ATP)通道激活介导的。
