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1 Department of Medicine and Pharmacology and Toxicology, Michigan State University, , East Lansing, Michigan, USA
* To whom correspondence should be addressed. E-mail: donna.wang{at}ht.msu.edu.
To determine the role of endothelin-1 (ET-1) and its receptors in regulation of calcitonin gene-related peptide (CGRP) release, male Wistar rats were divided into six groups and subjected to the following treatments for 1 week with or without ABT-627 (an ETA receptor antagonist, 5 mg/kg/day in drinking water) or A-192621 (an ETB receptor antagonist, 30 mg/kg/day by oral gavage): control (Con), ET-1 (5 ng/kg/min 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 to Con (104 ± 6), ET1 (106 ± 3), Con + ABT-627 (104 ± 3), and ET1 + ABT-627 (100 ± 3) groups. IV administration of CGRP8-37 (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 to Con (4 ± 1), Con-ABT-627 (4 ± 1), and ET-1 + ABT-627 (5 ± 1) groups. Plasma CGRP levels (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 to 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 (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 to 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 ETA receptor, which plays a compensatory role in preventing ET-1-induced elevation in blood pressure.
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