Selective antihypertensive action of moxonidine is mediated mainly by I1-imidazoline receptors in the rostral ventrolateral medulla.
Selective antihypertensive action of moxonidine is mediated mainly by I1-imidazoline receptors in the rostral ventrolateral medulla.
复制标题
DOI：
10.1097/00005344-199424001-00002
复制
发表时间：
1994
影响因子：
3
通讯作者：
M. Haxhiu;I. Dreshaj;S. Schäfer;P. Ernsberger
中科院分区：
文献类型：
--
作者：
M. Haxhiu;I. Dreshaj;S. Schäfer;P. Ernsberger
延髓头端腹外侧区（RVLM）是维持血管张力的主要区域，也是中枢降压药的作用部位。体外[125 I] p-碘可乐定结合研究表明，莫索尼定对RVLM中的I1-咪唑啉的选择性高于α 2-肾上腺素能受体。我们确定efaroxan和SK&F 86466作为选择性的I1-和α 2-拮抗剂，分别。我们测试了莫索尼定在自发性高血压大鼠（SHR）RVLM内对I1-咪唑啉或α 2-肾上腺素能受体的作用，并确定RVLM是否介导全身莫索尼定的作用。将SHR麻醉、麻痹和通气，并通过测试对2 nmol谷氨酸的升压反应来定位RVLM。为了测试I1或α 2是否介导莫索尼定的肿胀作用，在4 nmol莫索尼定之前15分钟给予I1/α 2拮抗剂efaroxan（4 nmol）或α 2阻断剂SK&F 86466（10 nmol）。Efaroxan升高血压，取消莫索尼定的作用，而α 2-阻断SK&F 86466轻微降低血压，只有部分衰减莫索尼定的作用。静脉注射莫索尼定（40 μ g/kg）的降压作用在10分钟内被RVLM微量注射10 nmol依法克生逆转。先前双侧RVLM微量注射efaroxan（10 nmol，80 nl/部位）可阻止静脉注射莫索尼定（40 μ g/kg）的消肿作用。药代动力学研究表明，在峰值血管降压反应（注射后8分钟），[3 H]莫索尼定从注射部位扩散不到1 mm。莫索尼定是一种中枢作用的抗高血压药，对RVLM中的I1-咪唑啉受体具有选择性作用。
The rostral ventrolateral medulla (RVLM) is the primary region maintaining vasomotor tone, and a site of action for central antihypertensive agents. In vitro [125I]p-iodoclonidine binding studies showed that moxonidine was selective for I1-imidazoline over alpha 2-adrenergic receptors in the RVLM. We identified efaroxan and SK&F 86466 as selective I1- and alpha 2-antagonists, respectively. We tested moxonidine's action within the RVLM of spontaneously hypertensive rats (SHRs) on I1-imidazoline or alpha 2-adrenergic receptors, and determined whether the RVLM mediates the action of systemic moxonidine. SHRs were anesthetized, paralyzed, and ventilated and the RVLM was localized by testing for a pressor response to 2 nmol glutamate. To test whether I1 or alpha 2 mediates hypotensive effects of moxonidine, the I1/alpha 2 antagonist efaroxan (4 nmol) or the alpha 2-blocker SK&F 86466 (10 nmol) was administered 15 min before 4 nmol moxonidine. Efaroxan elevated blood pressure and abolished the action of moxonidine, whereas alpha 2-blockade with SK&F 86466 slightly lowered blood pressure and only partially attenuated moxonidine's effect. The depressor effect of intravenous moxonidine (40 micrograms/kg) was reversed within 10 min by microinjection of 10 nmol efaroxan into the RVLM. Prior bilateral microinjections of efaroxan (10 nmol in 80 nl/site) into the RVLM prevented the hypotensive action of moxonidine given i.v. (40 micrograms/kg). Pharmacokinetic studies showed that at the peak vasodepressor response (8 min post-injection), [3H]moxonidine spread less than 1 mm from the injection site. Moxonidine is a centrally acting antihypertensive with a selective action on I1-imidazoline receptors in RVLM.