In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 31, No. 1 ( 1998-01), p. 499-504
Abstract:
Sodium plays an important role in the pathogenesis and therapy of hypertension, a major risk factor for cardiovascular disease. This study investigated the involvement of endothelin in vascular alterations in salt-induced Dahl hypertension. Salt-sensitive (DS) and salt-resistant (DR) Dahl rats were treated with a high-sodium diet (NaCl 4%) with or without ET A receptor antagonist LU135252 for two months, and effects of treatments on systolic blood pressure, vascular endothelin-1 (ET-1) protein content, aortic hypertrophy, and vascular reactivity of isolated aortic rings were studied. In DS rats, a high-sodium diet increased systolic pressure (190±4 versus 152±2 mm Hg, P 〈 .05) and aortic ET-1 protein content (4.2-fold, P 〈 .0001) and induced aortic hypertrophy as assessed by tissue weight ( P 〈 .0001). Sodium diet markedly reduced NO-mediated endothelium-dependent relaxations to acetylcholine (49±4% versus 81±4%, P 〈 .0001) and contractions to ET-1 (92±7 versus 136±8% of KCl, P =.0011). ET-1 tissue levels were highly and inversely correlated with endothelium-dependent relaxations ( r =0.931, P 〈 .0001) and contractions to ET ( r =0.77, P =.0007). LU135252 treatment reduced systolic blood pressure only in part (168±3 versus 190±4 mm Hg. P 〈 .05) but normalized sodium-induced changes of vascular reactivity, tissue ET-1 protein content, and vascular structure ( P 〈 .001 versus sodium). None of these effects were observed in DR rats. These results suggest that ET-1 acts as a local mediator of vascular dysfunction and aortic hypertrophy in Dahl salt-induced hypertension. ET A receptor antagonism may have therapeutic potential for lowering vascular ET-1 content, improving endothelial function, and preventing structural changes in salt-sensitive hypertension.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/01.HYP.31.1.499
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1998
detail.hit.zdb_id:
2094210-2
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