Wang Youping, Wang Donna H
Dept. of Medicine, B316 Clinical Center, Michigan State University, East Lansing, MI 48824, USA.
Am J Physiol Heart Circ Physiol. 2004 Oct;287(4):H1868-74. doi: 10.1152/ajpheart.00241.2004. Epub 2004 Jun 17.
To determine the role of endothelin-1 (ET-1) and its receptors in the regulation of calcitonin gene-related peptide (CGRP) release, male Wistar rats were divided into six groups and subjected to the following treatments for 1 wk with or without ABT-627 (an ET(A) receptor antagonist, 5 mg.kg(-1).day(-1) in drinking water) or A-192621 (an ET(B)-receptor antagonist, 30 mg.kg(-1).day(-1) by oral gavage): control (Con), ET-1 (5 ng.kg(-1).min(-1) iv), Con + ABT-627, Con + A-192621, ET-1 + ABT-627, and ET-1 + A-192621. Baseline mean arterial pressure (MAP, mmHg) was higher (P < 0.05) in Con + A-192621 (122 +/- 4) and ET-1 + A-192621 (119 +/- 4) groups compared with Con (104 +/- 6), ET1 (106 +/- 3), Con + ABT-627 (104 +/- 3), and ET1 + ABT-627 (100 +/- 3) groups. Intravenous administration of CGRP(8-37) (a CGRP receptor antagonist, 1 mg/kg) increased MAP (P < 0.05) in ET-1 (13 +/- 1), Con + A-192621 (12 +/- 1), and ET-1 + A-192621 (15 +/- 3) groups compared with Con (4 +/- 1), Con-ABT-627 (4 +/- 1), and ET-1 + ABT-627 (5 +/- 1) groups. Plasma CGRP levels (in pg/ml) were increased (P < 0.05) in ET-1 (57.5 +/- 6.1), Con + A-192621 (53.9 +/- 3.4), and ET-1 + A-192621 (60.4 +/- 3.0) groups compared with Con (40.4 +/- 1.6), Con + ABT-627 (40.0 +/- 2.9), and ET-1 + ABT-627 (42.6 +/- 1.9) groups. Plasma ET-1 levels (in pg/ml) were higher (P < 0.05) in ET-1 (2.8 +/- 0.2), ET-1 + ABT-627 (3.2 +/- 0.4), Con + A-192621 (3.3 +/- 0.4), and ET-1 + A-192621 (4.6 +/- 0.3) groups compared with Con (1.1 +/- 0.2) and Con-ABT-627 (1.3 +/- 0.2) groups. Therefore, our data show that ET-1 infusion leads to increased CGRP release via activation of the ET(A) receptor, which plays a compensatory role in preventing ET-1-induced elevation in blood pressure.
为了确定内皮素 -1（ET -1）及其受体在降钙素基因相关肽（CGRP）释放调节中的作用，将雄性Wistar大鼠分为六组，并进行以下处理1周，同时给予或不给予ABT -627（一种ET(A)受体拮抗剂，饮用水中浓度为5 mg·kg⁻¹·d⁻¹）或A -192621（一种ET(B)受体拮抗剂，经口灌胃剂量为30 mg·kg⁻¹·d⁻¹）：对照组（Con）、ET -1组（5 ng·kg⁻¹·min⁻¹静脉注射）、Con + ABT -627组、Con + A -192621组、ET -1 + ABT -627组和ET -1 + A -192621组。与Con组（104 ± 6）、ET1组（106 ± 3）、Con + ABT -627组（104 ± 3）和ET1 + ABT -627组（100 ± 3）相比，Con + A -192621组（122 ± 4）和ET -1 + A -192621组（119 ± 4）的基线平均动脉压（MAP，mmHg）更高（P < 0.05）。与Con组（4 ± 1）、Con - ABT -627组（4 ± 1）和ET -1 + ABT -627组（5 ± 1）相比，静脉注射CGRP(8 - 37)（一种CGRP受体拮抗剂，1 mg/kg）可使ET -1组（13 ± 1）、Con + A -192621组（12 ± 1）和ET -1 + A -192621组（15 ± 3）的MAP升高（P < 0.05）。与Con组（40.4 ± 1.6）、Con + ABT -627组（40.0 ± 2.9）和ET -1 + ABT -627组（42.6 ± 1.9）相比，ET -1组（57.5 ± 6.1）、Con + A -192621组（53.9 ± 3.4）和ET -1 + A -192621组（60.4 ± 3.0）的血浆CGRP水平（pg/ml）升高（P < 0.05）。与Con组（1.1 ± 0.2）和Con - ABT -627组（1.3 ± 0.2）相比，ET -1组（2.8 ± 0.2）、ET -1 + ABT -627组（3.2 ± 0.4）、Con + A -192621组（3.3 ± 0.4）和ET -1 + A -192621组（4.6 ± 0.3）的血浆ET -1水平（pg/ml）更高（P < 0.05）。因此，我们的数据表明，输注ET -1通过激活ET(A)受体导致CGRP释放增加，ET(A)受体在预防ET -1诱导的血压升高中起代偿作用。
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