Low sodium diet inhibits the local counter-regulator effect of angiotensin-(1-7) on angiotensin II.

Abstract:

OBJECTIVE:The heptapeptide angiotensin-(1-7) [Ang-(1-7)] has been identified as a versatile, endogenous inhibitor of the renin-angiotensin system (RAS). As the therapeutic response to exogenous RAS inhibitors, such as AT1 receptor antagonists, is altered by changes in salt intake, we investigated the effect of a low, normal and high sodium diet on the antagonism of Ang II by Ang-(1-7). The role of angiotensin receptor subtypes and the endothelium was assessed. METHODS:Male Wistar rats received a normal sodium (0.3% NaCl), high sodium (2.0% NaCl) or low sodium (0.05% NaCl) diet for 10 days. Vascular responses were assessed ex vivo in thoracic aortic rings in the presence of the nitric oxide (NO) inhibitor N-monomethyl-l-arginine (l-NMMA) to avoid aspecific vasodilator effects of Ang-(1-7). RESULTS:After a normal or high salt diet, Ang-(1-7) significantly decreased maximal Ang II-induced vascular constrictions by 40-50%. After a low salt diet this non-competitive antagonism disappeared. The AT2 receptor antagonist PD 123319 and the Ang-(1-7) receptor antagonist A779 attenuated the effect of Ang-(1-7) found in rats fed with a normal or high sodium diet. Further, removal of endothelium and pretreatment with the prostaglandin synthesis inhibitor indomethacin (10 mol/l) abolished the non-competitive antagonism by Ang-(1-7). CONCLUSION:Ang-(1-7) elicits a specific, endothelium-dependent and non-competitive antagonism of Ang II, which involves AT2 and Ang-(1-7) receptors but is independent of NO production. This non-competitive antagonism of Ang-(1-7) is abolished by a low sodium intake in normotensive rats, suggesting that it serves as a negative feedback towards Ang II in response to an altered sodium intake.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Roks AJ,Nijholt J,van Buiten A,van Gilst WH,de Zeeuw D,Henning RH

doi

10.1097/00004872-200412000-00018

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

2355-61

issue

12

eissn

0263-6352

issn

1473-5598

pii

00004872-200412000-00018

journal_volume

22

pub_type

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