期刊
REGULATORY PEPTIDES
卷 127, 期 1-3, 页码 101-110出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.regpep.2004.10.013
关键词
renin-angiotensin system; NADPH oxidase; heart; AT(1) receptor
The cardiovascular role of angiotensin-(1-7), especially in the functional and metabolic alterations associated with ischemia-reperfusion (IR), is still not clearly defined. Our objective was to evaluate the cardiac effects of angiotensin-(1-7), the receptors involved, and their relationships with NADPH oxidase activation under non-ischemic conditions and, during an ischemia-reperfusion sequence. Isolated perfused rat hearts underwent 45 min of non-ischemic perfusion, or 30 min of global ischemia followed by 30 min of reperfusion. Angiotensin-(1-7) and/or AT(1) receptor blocker losartan or angiotensin-(1-7) receptor antagonist (D-Ala(7))-angiotensin-(1-7) were perfused. Our results showed that angiotensin-(1-7) was without effect at low concentrations (10(-10) to 10(-7) M). At a pharmacological concentration, 0.5 muM angiotensin-(1-7) induced vasoconstriction, which was antagonised by losartan. After ischemia, we noted a partial recovery of functional parameters, which was not modified by any of the treatments. The expression of AT(1) receptor mRNA was increased by ischemia-reperfusion, except in (D-Ala(7))-angiotensin-(1-7) treated hearts. Angiotensin-(1-7) further increased the AT(1) expression. NADPH oxidase activity was enhanced in 0.5 muM angiotensin-(1-7)-treated hearts subjected to ischemia-reperfusion, this effect was totally reversed by losartan. This is the first time that it has been shown that, in the heart, angiotensin-(1-7) at pharmacological concentration activates NADPH oxidase, an enzyme thought to be involved in several angiotensin 11 effects. (C) 2004 Elsevier B.V. All rights reserved.
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