Katusić Z S
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905.
Am J Physiol. 1992 May;262(5 Pt 2):H1557-62. doi: 10.1152/ajpheart.1992.262.5.H1557.
Experiments were designed to characterize the mechanism of vasopressin action in small arteries of brain stem and cerebrum and to determine the role of L-arginine pathway in reactivity of these vessels to vasopressin. Secondary branches of canine basilar arteries (425 +/- 63 microns ID, n = 6) and middle cerebral arteries (466 +/- 30 microns ID, n = 6) were dissected and mounted on glass microcannulas in organ chambers. Changes in intraluminal diameter of the pressurized arteries were measured using a video dimension analyzer. Vasopressin caused endothelium-dependent relaxation in the brain stem arteries [-log half-maximal effective concentration (EC50) = 9.2 +/- 0.4, n = 5] but not in the branches of middle cerebral arteries. In contrast, bradykinin caused identical endothelium-dependent relaxations in arteries of both regions (-log EC50 = 8.0 +/- 0.2, n = 5, and 7.7 +/- 0.1, n = 4 for brain stem and cerebrum, respectively). Relaxations to vasopressin (but not to bradykinin) were reduced in the presence of V1-vasopressinergic antagonist [1-(beta-mercapto-beta-cyclopentamethylenepropionic acid),2-(O-methyl)tyrosine]arginine vasopressin [d(CH2)5-Tyr(Me)AVP;10(-7) M], pertussin toxin (100 ng/ml), and NG-monomethyl-L-arginine (L-NMMA; 10(-4) M). The inhibitory effect of L-NMMA was prevented by L-arginine (3 x 10(-4) M) but not D-arginine (3 x 10(-4) M). These studies suggest that vasopressin causes endothelium-dependent relaxation in canine brain stem arteries. The effect of the neuropeptide appears to be mediated by activation of endothelial V1-vasopressinergic receptors coupled to nitric oxide synthase. This signal transduction pathway is not functional in endothelial cells of branches of middle cerebral arteries.
实验旨在表征血管加压素在脑干和大脑小动脉中的作用机制，并确定L-精氨酸途径在这些血管对血管加压素反应性中的作用。解剖犬基底动脉（内径425±63微米，n = 6）和大脑中动脉（内径466±30微米，n = 6）的二级分支，并安装在器官腔室的玻璃微插管上。使用视频尺寸分析仪测量加压动脉的管腔内直径变化。血管加压素引起脑干动脉内皮依赖性舒张[-log半数最大有效浓度（EC50）= 9.2±0.4，n = 5]，但在大脑中动脉分支中未引起。相反，缓激肽在两个区域的动脉中引起相同的内皮依赖性舒张（脑干和大脑的-log EC50分别为8.0±0.2，n = 5和7.7±0.1，n = 4）。在存在V1血管加压素能拮抗剂[1-（β-巯基-β-环戊亚甲基丙酸），2-（O-甲基）酪氨酸]精氨酸血管加压素[d（CH2）5-Tyr（Me）AVP；10-7 M]、百日咳毒素（100 ng/ml）和NG-单甲基-L-精氨酸（L-NMMA；10-4 M）的情况下，对血管加压素（而非缓激肽）的舒张作用减弱。L-精氨酸（3×10-4 M）可阻止L-NMMA的抑制作用，但D-精氨酸（3×10-4 M）则不能。这些研究表明，血管加压素在犬脑干动脉中引起内皮依赖性舒张。该神经肽的作用似乎是由与一氧化氮合酶偶联的内皮V1血管加压素能受体的激活介导的。该信号转导途径在大脑中动脉分支的内皮细胞中不起作用。
