Kawada Toru, Shimizu Shuji, Yamamoto Hiromi, Miyamoto Tadayoshi, Shishido Toshiaki, Sugimachi Masaru
Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
Life Sci. 2017 Dec 1;190:103-109. doi: 10.1016/j.lfs.2017.09.038. Epub 2017 Sep 28.
Moxonidine is a centrally acting antihypertensive agent with a selectivity to I-imidazoline receptors higher than that to α-adrenergic receptors. The present study aimed to quantify a peripheral effect of moxonidine on carotid sinus baroreflex-mediated sympathetic arterial pressure (AP) regulation separately from its central effect.
In eight anesthetized Wistar rats, changes in efferent sympathetic nerve activity (SNA) and AP in response to a carotid sinus pressure input were compared before and during an intravenous administration of moxonidine (100μgkg bolus followed by a continuous infusion at 200μg·kg·h).
Moxonidine significantly narrowed the range of the AP response (55.3±5.8 to 39.1±6.1mmHg, P<0.05) without changing the minimum AP (77.2±6.4 to 80.7±5.1mmHg, not significant). In the neural arc, moxonidine reduced the minimum SNA (56.6±5.9 to 29.7±6.2%, P<0.05) without affecting the range of the SNA response (45.3±5.5 to 40.2±5.0%, not significant). In the peripheral arc, moxonidine increased the intercept (3.0±8.5 to 51.1±7.2mmHg, P<0.01) and reduced the slope (1.28±0.06 to 0.92±0.15mmHg/%, P<0.05).
Moxonidine increased AP at any given SNA, suggesting that the peripheral vasoconstrictive effect is stronger than generally recognized. The peripheral vasoconstrictive effect of moxonidine may partly offset the vasodilatory effect attained by centrally-mediated sympathoinhibition.
莫索尼定是一种中枢性降压药,对I-咪唑啉受体的选择性高于α-肾上腺素能受体。本研究旨在分别量化莫索尼定的外周效应及其对颈动脉窦压力反射介导的交感神经动脉血压(AP)调节的中枢效应。
在8只麻醉的Wistar大鼠中,比较静脉注射莫索尼定(100μg/kg推注,随后以200μg·kg·h持续输注)前后,传出交感神经活动(SNA)和AP对颈动脉窦压力输入的反应变化。
莫索尼定显著缩小了AP反应范围(从55.3±5.8降至39.1±6.1mmHg,P<0.05),但未改变最低AP(从77.2±6.4降至80.7±5.1mmHg,无显著差异)。在神经反射弧中,莫索尼定降低了最低SNA(从56.6±5.9降至29.7±6.2%,P<0.05),但不影响SNA反应范围(从45.3±5.5降至40.2±5.0%,无显著差异)。在周围反射弧中,莫索尼定增加了截距(从3.0±8.5升至51.1±7.2mmHg,P<0.01)并降低了斜率(从1.28±0.06降至0.92±0.15mmHg/%,P<0.05)。
莫索尼定在任何给定的SNA水平下均增加了AP,表明其外周血管收缩作用比一般认为的更强。莫索尼定的外周血管收缩作用可能部分抵消了中枢介导的交感神经抑制所产生的血管舒张作用。