Effects of angiotensin IV and angiotensin-(1-7) on basal and angiotensin II-stimulated cytosolic Ca2+ in mesangial cells

This study analyzed the influence of two main metabolites of angiotensin II , angiotensin IV and angiotensin-(1-7), on basal and angiotensin II-depende nt [Ca2+](i) in rat mesangial cells. Angiotensin IV behaved as a weak agoni st. Its effects were abolished by angiotensin AT(1) receptor antagonists. T reatment with angiotensin II abolished the effect of a subsequent treatment with angiotensin IV whereas two successive angiotensin IV-dependent [Ca2+] (i) peaks were obtained. Angiotensin II increased [Ca2+](i) in a Ca2+-free medium whereas angiotensin IV was inactive. Leucine-valine-valine-hemorphin 7, a hemorphin specific for the angiotensin AT(4) receptor, was devoid of any agonistic or antagonistic effect. In contrast, angiotensin-(1-7), if wi thout influence on basal [Ca2+](i) inhibited angiotensin II- and angiotensi n IV-dependent [Ca2+](i) increases. Total inhibition of the angiotensin IV effect was obtained whereas association of angiotensin-(1-7) to 8-(NN-dieth ylamino)-octyl-3,4,5-trimethoxybenzoate, an inhibitor of inositol phosphate -mediated Ca2+ release, was necessary to suppress the effect of angiotensin II. These results provide evidence that angiotensin II metabolites may par ticipate in the control of [Ca2+](i) in mesangial cells at the initial stag e of binding to the angiotensin AT(1) receptors. (C) 2001 Elsevier Science B.V. All rights reserved.