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

Roks, A. J. M., Nijholt, J., van Buiten, A., van Gilst, W. H., de Zeeuw, D. & Henning, R. H., Dec-2004, In : Journal of Hypertension. 22, 12, p. 2355-2361 7 p.

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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 AT, 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-G-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 noncompetitive antagonism disappeared. The AT(2) 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(-5) 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 AT(2) 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 11 in response to an altered sodium intake. (C) 2004 Lippincott Williams Wilkins.

Original languageEnglish
Pages (from-to)2355-2361
Number of pages7
JournalJournal of Hypertension
Volume22
Issue number12
Publication statusPublished - Dec-2004

    Keywords

  • Angiotensin I, Angiotensin II, Angiotensin II Type 2 Receptor Blockers, Angiotensin Receptor Antagonists, Animals, Aorta, Thoracic, Diet, Sodium-Restricted, Endothelium, Vascular, In Vitro Techniques, Male, Peptide Fragments, Rats, Rats, Wistar, Receptor, Angiotensin, Type 2, Receptors, Angiotensin, Vasoconstriction

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