Fauvel J P, Najem R, Maakel N, Pozet N, Laville M
Department of Nephrology and Hypertension, CNRS URA 606, Hôpital Edouard Herriot, Lyon, France.
J Cardiovasc Pharmacol. 1998 Sep;32(3):495-9. doi: 10.1097/00005344-199809000-00022.
Moxonidine is an imidazoline I1-receptor agonist that centrally acts by reducing the sympathetic tone. Furthermore, proximal tubular I1-receptors have been isolated in human kidneys, but their natriuretic effects have never been demonstrated. Because stress tests elicited a sympathetically mediated increase in blood pressure and in sodium reabsorption, the aim of this study was to assess the effects of moxonidine (0.4 mg/day; 1 month) on stress-induced cardiovascular response and renal sodium handling in hypertensives, in a double-blind, crossover, placebo-controlled study. The stress test used is an efficient and reproducible computerized version of Stroop's stress test. During the experimental sessions, both rest and stress renal functional parameters were determined: glomerular filtration rate (inulin clearance), renal plasma flow (para-aminohippurate clearance), filtration fraction, sodium excretion, and segmental sodium tubular reabsorption (lithium clearance). During the placebo phase, stress induced a significant increase in systolic blood pressure (deltaSBP; 15.8+/-10.7 mm Hg) and diastolic blood pressure (deltaDBP; 8.2+/-6.1 mm Hg). During stress, glomerular filtration rate tended to decrease, whereas renal plasma flow significantly decreased, resulting in a significant increase in filtration fraction. Despite the increase in BP, stress induced a decrease in sodium excretion that was mainly due to a nonsignificant increase in sodium reabsorption in the proximal parts of the tubules. Moxonidine significantly reduced rest and stress BP, but the stress cardiovascular reactivity was not altered. At rest, renal function was well preserved by the treatment. Stress-induced modifications in renal function and sodium handling were not altered by the treatment. In conclusion, moxonidine reduced rest and stress-induced peak BP and preserved basal renal function. The study failed to demonstrate any effect of moxonidine either on basal renal sodium handling or on stress-induced increase in sodium reabsorption.
莫索尼定是一种咪唑啉I1受体激动剂，通过降低交感神经张力发挥中枢作用。此外，已在人肾脏中分离出近端肾小管I1受体，但其利钠作用尚未得到证实。由于应激试验可引起交感神经介导的血压升高和钠重吸收增加，本研究旨在通过一项双盲、交叉、安慰剂对照研究，评估莫索尼定（0.4毫克/天；1个月）对高血压患者应激诱导的心血管反应和肾脏钠处理的影响。所采用的应激试验是一种高效且可重复的计算机化斯特鲁普应激试验版本。在实验过程中，测定了静息和应激状态下的肾功能参数：肾小球滤过率（菊粉清除率）、肾血浆流量（对氨基马尿酸清除率）、滤过分数、钠排泄以及节段性肾小管钠重吸收（锂清除率）。在安慰剂阶段，应激导致收缩压显著升高（收缩压变化值；15.8±10.7毫米汞柱）和舒张压显著升高（舒张压变化值；8.2±6.1毫米汞柱）。应激期间，肾小球滤过率有下降趋势，而肾血浆流量显著下降，导致滤过分数显著增加。尽管血压升高，但应激导致钠排泄减少，这主要是由于肾小管近端钠重吸收无显著增加所致。莫索尼定显著降低了静息和应激状态下的血压，但应激心血管反应性未改变。在静息状态下，治疗可很好地保留肾功能。治疗未改变应激诱导的肾功能和钠处理变化。总之，莫索尼定降低了静息和应激诱导的血压峰值，并保留了基础肾功能。该研究未能证明莫索尼定对基础肾脏钠处理或应激诱导的钠重吸收增加有任何作用。
