| Contrasting effects of intervention with ETA and ETB receptor antagonists in hypertension induced by angiotensin II and high-salt diet. | |
| | |
MedLine Citation:
|
PMID: 20725138 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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 ETA (ABT-627) or ETB (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 ETA receptor signaling in maintaining AngII-HS hypertension and suggest that including ETB receptor blockade in therapeutic approaches to treating hypertension would be ineffective or even counterproductive. |
| | |
Authors:
|
Erika I Boesen; Jennifer S Pollock; David M Pollock |
Related Documents
:
|
20019328 - Angiotensin ii induces a region-specific hyperplasia of the ascending aorta through reg... 20836698 - Lentiviral-human heme oxygenase targeting endothelium improved vascular function in ang... 17086018 - Angiotensin receptor blockade improves vascular compliance in healthy normotensive elde... 22326878 - Dp/dt(max) - a measure of 'baroinometry' 7366248 - Relationship between the measured and calculated colloid osmotic pressure of plasma and... 10423638 - The effects of delapril in combination with indapamide on glomerular filtration rate in... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Canadian journal of physiology and pharmacology Volume: 88 ISSN: 1205-7541 ISO Abbreviation: Can. J. Physiol. Pharmacol. Publication Date: 2010 Aug |
Date Detail:
|
Created Date: 2010-08-20 Completed Date: 2011-01-13 Revised Date: 2011-07-26 |
Medline Journal Info:
|
Nlm Unique ID: 0372712 Medline TA: Can J Physiol Pharmacol Country: Canada |
Other Details:
|
Languages: eng Pagination: 802-7 Citation Subset: IM |
Affiliation:
|
Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Boulevard, Augusta, GA 30912, USA. eboesen@mcg.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acute Kidney Injury
/
etiology,
physiopathology,
urine Angiotensin II / pharmacology* Animals Antihypertensive Agents / pharmacology, therapeutic use Blood Pressure / drug effects, physiology Hypertension / chemically induced*, complications, drug therapy*, physiopathology Male Nitrates / blood, urine Nitrites / blood, urine Pyrrolidines / pharmacology, therapeutic use Rats Rats, Sprague-Dawley Receptor, Endothelin A / antagonists & inhibitors* Receptor, Endothelin B / antagonists & inhibitors* Sodium Chloride, Dietary / pharmacology* Treatment Outcome |
| Grant Support | |
ID/Acronym/Agency:
|
HL64776/HL/NHLBI NIH HHS; HL74167/HL/NHLBI NIH HHS; P01 HL069999-09/HL/NHLBI NIH HHS; P01 HL095499-01A1/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/A 127722; 0/A 192621; 0/Antihypertensive Agents; 0/Nitrates; 0/Nitrites; 0/Pyrrolidines; 0/Receptor, Endothelin A; 0/Receptor, Endothelin B; 0/Sodium Chloride, Dietary; 11128-99-7/Angiotensin II |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Beta-arrestin-1 mediates the endothelin-1-induced activation of Akt and integrin-linked kinase.
Next Document: Endothelin signaling via guanine exchange factor C3G in renal glomerular mesangial cells.