Okada Shoshiro, Murakami Yoshinori, Nakamura Kumiko, Yokotani Kunihiko
Department of Pharmacology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
Eur J Pharmacol. 2002 Dec 13;457(1):29-35. doi: 10.1016/s0014-2999(02)02652-3.
The present study was designed to characterize the vasopressin receptor subtype involved in the vasopressin-induced activation of the central sympatho-adrenomedullary outflow using urethane-anesthetized rats. Intracerebroventricularly (i.c.v.) administered vasopressin (0.1, 0.2 and 0.5 nmol/animal) dose-dependently elevated plasma levels of adrenaline and noradrenaline (adrenaline>noradrenaline). The vasopressin (0.2 nmol/animal)-induced elevation of both catecholamines was significantly attenuated by [d(CH(2))(5)(1),Tyr(Me)(2),Arg(8)]-vasopressin, a selective vasopressin V(1) receptor antagonist, in a dose-dependent manner (0.1 and 0.2 nmol/animal, i.c.v.). The same doses (0.1 and 0.2 nmol/animal, i.c.v.) of [1-adamantaneacetyl(1),D-Tyr(Et)(2),Val(4),Abu(6), Arg(8,9)]-vasopressin, a potent vasopressin V(2) receptor antagonist, had no effect; however, a large dose of this antagonist (1.6 nmol/animal, i.c.v.) effectively reduced the vasopressin-induced elevation of catecholamines. On the other hand, [5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine], a selective vasopressin V(2) receptor antagonist (5 and 10 nmol/animal, i.c.v.), had no effect on the vasopressin-induced elevation of catecholamines. The vasopressin-induced elevation of catecholamines was abolished by indomethacin, an inhibitor of cyclooxygenase (1.2 micromol/animal, i.c.v.). These results suggest that the vasopressin activates the central sympatho-adrenomedullary outflow by brain vasopressin V(1) receptor- and cyclooxygenase-dependent mechanisms in rats.
本研究旨在利用氨基甲酸乙酯麻醉的大鼠，确定参与血管升压素诱导的中枢交感-肾上腺髓质传出激活的血管升压素受体亚型。脑室内（i.c.v.）注射血管升压素（0.1、0.2和0.5 nmol/只动物）可剂量依赖性地提高血浆肾上腺素和去甲肾上腺素水平（肾上腺素>去甲肾上腺素）。选择性血管升压素V(1)受体拮抗剂[d(CH(2))(5)(1),Tyr(Me)(2),Arg(8)]-血管升压素（0.1和0.2 nmol/只动物，i.c.v.）可剂量依赖性地显著减弱血管升压素（0.2 nmol/只动物）诱导的两种儿茶酚胺水平升高。相同剂量（0.1和0.2 nmol/只动物，i.c.v.）的强效血管升压素V(2)受体拮抗剂[1-金刚烷乙酰基(1),D-Tyr(Et)(2),Val(4),Abu(6),Arg(8,9)]-血管升压素无作用；然而，大剂量的这种拮抗剂（1.6 nmol/只动物，i.c.v.）可有效降低血管升压素诱导的儿茶酚胺水平升高。另一方面，选择性血管升压素V(2)受体拮抗剂[5-二甲基氨基-1-[4-(2-甲基苯甲酰氨基)苯甲酰基]-2,3,4,5-四氢-1H-苯并氮杂卓]（5和10 nmol/只动物，i.c.v.）对血管升压素诱导的儿茶酚胺水平升高无作用。环氧化酶抑制剂吲哚美辛（1.2 μmol/只动物，i.c.v.）可消除血管升压素诱导的儿茶酚胺水平升高。这些结果表明，血管升压素通过大鼠脑内血管升压素V(1)受体和环氧化酶依赖性机制激活中枢交感-肾上腺髓质传出。
