In:
Canadian Journal of Physiology and Pharmacology, Canadian Science Publishing, Vol. 88, No. 8 ( 2010-08), p. 802-807
Abstract:
Endothelin (ET) receptor antagonists are antihypertensive and renoprotective in angiotensin II (AngII)-induced hypertension if administered when AngII infusion commences, but their effects on established hypertension are poorly understood. We therefore tested the effects of intervening with an ET A (ABT-627) or ET B (A-192621) receptor antagonist after establishing hypertension with AngII (65 ng/min s.c.) plus 8% NaCl diet (AngII–HS) in rats. Prior to administration of ABT-627, AngII–HS and AngII–HS plus ABT-627 groups displayed robust hypertension (mean arterial pressure (MAP), 170 ± 5 and 165 ± 5 mm Hg versus 110 ± 3 mm Hg in normal salt control rats at day 7, P 〈 0.05). Administering ABT-627 from day 8 of AngII–HS treatment prevented further rises in MAP (168 ± 5 and 191 ± 3 mm Hg at day 13 in AngII–HS plus ABT-627 and AngII–HS, P 〈 0.001), without blunting the significant increases in urinary protein (19-fold), albumin (25-fold), or MCP-1 excretion (6- to 8-fold) or the reduction in creatinine clearance. Administering A-192621 from day 8 mildly exacerbated AngII–HS induced hypertension (P 〈 0.05 for AngII–HS versus AngII–HS plus A-192621 on days 11 and 12 only) and reduced plasma nitrite/nitrate concentration (P 〈 0.05), without affecting proteinuria, albuminuria, or creatinine clearance. These results confirm the importance of ET A receptor signaling in maintaining AngII–HS hypertension and suggest that including ET B receptor blockade in therapeutic approaches to treating hypertension would be ineffective or even counterproductive.
Type of Medium:
Online Resource
ISSN:
0008-4212
,
1205-7541
Language:
English
Publisher:
Canadian Science Publishing
Publication Date:
2010
detail.hit.zdb_id:
2004356-9
