Endothelin and ETA receptors in long-term arterial pressure homeostasis in conscious nonhuman primates
Endothelin and ETA receptors in long-term arterial pressure homeostasis in conscious nonhuman primates
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DOI：
10.1152/ajpregu.2000.279.5.r1701
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发表时间：
2000-11-01
影响因子：
2.8
通讯作者：
Cox, BF
中科院分区：
文献类型：
--
作者：
Reinhart, GA;Preusser, LC;Cox, BF
本研究旨在量化非人灵长类动物在正常条件下内源性内皮素-1 （ET-1）和ETA受体对动脉压调节的长期贡献。因此，在控制条件下，在给予ETA选择性受体拮抗剂（ABT-627; 5 mg/kg，每天口服2次，4天）和治疗后6天，使用遥测技术测量有意识食蟹猴24小时/天的平均动脉压（MAP）和心率。系统性ETA阻断使MAP（24小时）在第1天和第4天分别从89 +/- 3 mmHg降低到82 +/- 2和79 +/- 2 mmHg。随后，MAP在治疗后3天仍被抑制。在ABT-627治疗的第1天和第4天，心率分别从111 +/- 5次增加到122 +/- 4次和128 +/- 6次/分，并在治疗后3天保持高于对照组的水平。ABT-627治疗后（第4天）血浆ET-1浓度从1.0 +/- 0.3 pg/ml上升到1.9 +/- 0.4 pg/ml，但在治疗后4天降至对照组。这些数据表明，在有意识的非人灵长类动物中，内源性ET-1和ETA受体在动脉压和血浆ET-1水平的长期调节中具有重要的生理作用。
This study was designed to quantify the long-term contribution of endogenous endothelin-1 (ET-1) and ETA receptors to the regulation of arterial pressure under normal conditions in nonhuman primates. Therefore, mean arterial pressure (MAP) and heart rate were measured 24 h/day with the use of telemetry techniques in conscious cynomolgus monkeys under control conditions, during administration of an ETA selective receptor antagonist (ABT-627; 5 mg/kg, 2 times a day by mouth, 4 days), and a 6-day posttreatment period. Systemic ETA blockade reduced MAP (24 h) from 89 +/- 3 to 82 +/- 2 and 79 +/- 2 mmHg on days 1 and 4, respectively. Subsequently, MAP remained suppressed for 3 days posttreatment. Heart rate increased from 111 +/- 5 to 122 +/- 4 and 128 +/- 6 beats/min on days 1 and 4 of ABT-627, respectively, and remained above control for 3 days post-treatment. Plasma ET-1 concentration increased from 1.0 +/- 0.3 to 1.9 +/- 0.4 pg/ml in response to ABT-627 (day 4) but decreased to control values 4 days posttreatment. These data demonstrate a physiologically important role for endogenous ET-1 and ETA receptors in the long-term regulation of arterial pressure and plasma ET-1 levels in the conscious nonhuman primate.