Nicotine exposure, mimicked smoking, directly and indirectly enhanced protein kinase C activity in isolated canine basilar artery, resulting in enhancement of arterial contraction
Nicotine exposure, mimicked smoking, directly and indirectly enhanced protein kinase C activity in isolated canine basilar artery, resulting in enhancement of arterial contraction
复制标题
DOI：
10.1038/sj.jcbfm.9600016
复制
发表时间：
2005-03-01
影响因子：
6.3
通讯作者：
Terakawa, S
中科院分区：
文献类型：
--
作者：
Koide, M;Nishizawa, S;Terakawa, S
吸烟是脑血管疾病发病的重要危险因素。在香烟烟雾中的许多化合物中，尼古丁被认为对脑动脉张力影响最显着。本研究的目的是研究尼古丁对脑动脉张力调节的确切药理学作用。为了模拟吸烟，在等长张力研究中给予相当于习惯性吸烟者血清水平的低浓度尼古丁（10（-6）mol/L）1小时，在使用培养的血管内皮细胞（VEC）的研究中给予24小时。采用犬基底动脉，在等长张力研究中检测尼古丁对尿苷5 '-三磷酸（UTP）诱导的血管收缩的影响。用酶免疫分析法测定犬基底动脉蛋白激酶C（PKC）活性。采用荧光指示剂二氨基荧光素-FM二乙酸酯（DAF-FM/DA），通过内皮依赖性血管舒张和内皮细胞内源性一氧化氮（NO）合成来评估内皮功能。尼古丁显著增强UTP诱导的血管收缩和PKC活性，减弱内皮依赖性血管舒张和血管内皮细胞NO合成。由于PKC活性通过去内皮化本身而增加，尼古丁引起的内皮功能障碍增强了PKC活性。由于即使在去内皮化的动脉中，尼古丁也能进一步激活PKC，因此尼古丁直接影响平滑肌中的PKC活性。这些结果表明，尼古丁通过直接和间接激活PKC增强犬基底动脉的收缩反应。
Cigarette smoking is a significant risk factor in the incidence of cerebrovascular disorders. Among the many compounds in cigarette smoke, nicotine is considered to most significantly affect cerebral arterial tone. The purpose of this study is to investigate precise pharmacological effects of nicotine on the regulation of cerebral arterial tone. To mimic smoking, a low concentration of nicotine (10(-6) mol/L), which is equivalent to the serum level of habitual smokers, was treated for 1 hour in an isometric tension study and for 24 hours in a study using cultured vascular endothelial cells (VECs). Using the canine basilar artery, the effect of nicotine on uridine 5'-triphosphate (UTP)-induced vasoconstriction was examined in the isometric tension study. Protein kinase C (PKC) activity in the canine basilar artery was measured by enzyme immunoassay. Endothelial function was assessed by endothelium-dependent vasodilatation and endogenous nitric oxide (NO) synthesis in VECs using a fluorescent indicator, diaminofluorescein-FM diacetate (DAF-FM/DA). Nicotine significantly enhanced UTP-induced contraction and PKC activity in the artery, and attenuated endothelium-dependent vasodilatation and NO synthesis in VECs. Because PKC activity was increased by de-endothelialization itself, endothelial dysfunction by nicotine enhances PKC activity. Because PKC was further activated by nicotine even in the de-endothelialized artery, nicotine directly affects PKC activities in smooth muscle. These results indicate that nicotine potentiates contractile response through direct and indirect PKC activation in the canine basilar artery.