Baskaya M K, Suzuki Y, Anzai M, Seki Y, Saito K, Takayasu M, Shibuya M, Sugita K
Department of Neurosurgery, Nagoya University School of Medicine, Japan.
J Cereb Blood Flow Metab. 1995 Sep;15(5):827-34. doi: 10.1038/jcbfm.1995.103.
The effect of human adrenomedullin on cerebral circulation was investigated in dogs in vivo and in vitro. Bolus administration of adrenomedullin or its homologous peptides, calcitonin gene-related peptide (CGRP) and amylin, into the vertebral artery induced a dose-dependent increase in vertebral blood flow. The potencies of adrenomedullin and CGRP were similar and approximately 100 times more than that of amylin. The effects of adrenomedullin and CGRP were inhibited by CGRP8-37, an antagonist of CGRP. In contrast to substance P, adrenomedullin did not induce an increase in blood flow after prior administration of CGRP. Pretreatment with either NG-nitro-L-arginine methyl ester or indomethacin did not affect the adrenomedullin-induced increase in blood flow. Intracisternal administration of adrenomedullin induced dilation of the basilar and other major cerebral arteries in a dose-dependent manner, accompanied by an increase in the concentration of cyclic AMP in the cerebrospinal fluid. Adrenomedullin also induced relaxation of isolated basilar and middle cerebral arterial rings. These data suggest that adrenomedullin induces vasodilation of cerebral arteries and an increase in vertebral blood by acting at CGRP receptors positively coupled to adenylate cyclase, and that these effects are not dependent on nitric oxide or prostaglandin formation.
在体内和体外实验中研究了人肾上腺髓质素对犬脑循环的影响。将肾上腺髓质素或其同源肽降钙素基因相关肽（CGRP）和胰淀素大剂量注入椎动脉可引起椎动脉血流量呈剂量依赖性增加。肾上腺髓质素和CGRP的效力相似，约为胰淀素的100倍。肾上腺髓质素和CGRP的作用被CGRP的拮抗剂CGRP8 - 37抑制。与P物质不同，在预先给予CGRP后，肾上腺髓质素不会引起血流量增加。用NG - 硝基 - L - 精氨酸甲酯或吲哚美辛预处理不会影响肾上腺髓质素诱导的血流量增加。脑池内注射肾上腺髓质素可引起基底动脉和其他主要脑动脉呈剂量依赖性扩张，同时脑脊液中环磷酸腺苷浓度增加。肾上腺髓质素还可引起离体基底动脉和大脑中动脉环舒张。这些数据表明，肾上腺髓质素通过作用于与腺苷酸环化酶正偶联的CGRP受体，诱导脑动脉血管舒张和椎动脉血流量增加，且这些作用不依赖于一氧化氮或前列腺素的形成。
