Dedeoğlu A, Fisher L A
Department of Pharmacology, University of Arizona College of Medicine, Tucson.
J Pharmacol Exp Ther. 1991 Dec;259(3):1027-34.
The mechanisms underlying the cardiovascular effects of central and peripheral administration of the 5-HT2 (serotonin) receptor agonist (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) were studied in conscious rats. Intravenous (10-1000 nmol/kg) and i.c.v. (3-300 nmol) administration of DOI produced dose-related elevations of arterial pressure without altering heart rate except after injection of the highest doses. Pretreatment with xylamidine tosylate, a 5-HT2 receptor antagonist that does not cross the blood-brain barrier, blocked the pressor response to i.v., but not i.c.v., administration of equivalent doses of DOI. Pretreatment with the vasopressin receptor antagonist d(CH2)5Tyr(Me)AVP significantly reduced the pressor response to i.c.v., but not i.v., administration of DOI. Prior ganglionic blockade with chlorisondamine amplified the pressor response to both i.v. and i.c.v. administration of DOI. Pretreatment with a combination of chlorisondamine, xylamidine and d(CH2)5Tyr(Me)AVP abolished the pressor response to i.c.v. administration of DOI. Thus, the pressor response to i.v. administration of DOI was mediated at sites outside the blood-brain barrier, most likely at vascular 5-HT2 receptors, and was not secondary to vasopressin release. Inappropriate heart rate changes attended the pressor responses to i.v. administration of DOI, suggesting an action at extravascular sites. The pressor response to i.c.v. administration of DOI resulted from a combination of vasopressin release, modulation of autonomic nervous outflow and some leakage into the periphery.
在清醒大鼠中研究了中枢和外周给予5-HT2（血清素）受体激动剂（±）-1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷盐酸盐（DOI）的心血管效应的潜在机制。静脉注射（10-1000 nmol/kg）和脑室内注射（3-300 nmol）DOI可引起剂量相关的动脉压升高，除注射最高剂量后外，心率无变化。用甲苯磺酸木拉米定预处理，一种不穿过血脑屏障的5-HT2受体拮抗剂，可阻断静脉注射等量DOI的升压反应，但不能阻断脑室内注射的升压反应。用血管加压素受体拮抗剂d（CH2）5Tyr（Me）AVP预处理可显著降低脑室内注射DOI的升压反应，但不能降低静脉注射的升压反应。事先用氯异吲哚胺进行神经节阻断可增强静脉注射和脑室内注射DOI的升压反应。用氯异吲哚胺、甲苯磺酸木拉米定和d（CH2）5Tyr（Me）AVP联合预处理可消除脑室内注射DOI的升压反应。因此，静脉注射DOI的升压反应是由血脑屏障外的部位介导的，最可能是血管5-HT2受体，且不是血管加压素释放的继发反应。静脉注射DOI的升压反应伴随有不适当的心率变化，提示在血管外部位有作用。脑室内注射DOI的升压反应是由血管加压素释放、自主神经流出的调节以及一些渗漏到外周共同作用的结果。
