Angiotensin II type 1 receptor blockade restores angiotensin-(1–7)-induced coronary vasodilation in hypertrophic rat hearts
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Data
2013
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Resumo
The aim of the present study was to investigate the coronary effects of Ang-(1–7) [angiotensin-(1–7)] in hypertrophic
rat hearts. Heart hypertrophy was induced by abdominal aorta CoA (coarctation). Ang-(1–7) and AVE 0991, a
non-peptide Mas-receptor agonist, at picomolar concentration, induced a significant vasodilation in hearts from
sham-operated rats. These effects were blocked by the Mas receptor antagonist A-779. Pre-treatment with L-NAME
(NG-nitro-L-arginine methyl ester) or ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinozalin-1-one) [NOS (NO synthase) and
soluble guanylate cyclase inhibitors respectively] also abolished the effect of Ang-(1–7) in control hearts. The
coronary vasodilation produced by Ang-(1–7) and AVE 0991 was completely blunted in hypertrophic hearts. Chronic
oral administration of losartan in CoA rats restored the coronary vasodilation effect of Ang-(1–7). This effect was
blocked by A-779 and AT2 receptor (angiotensin II type 2 receptor) antagonist PD123319. Acute pre-incubation with
losartan also restored the Ang-(1–7)-induced, but not BK (bradykinin)-induced, coronary vasodilation in hypertrophic
hearts. This effect was inhibited by A-779, PD123319 and L-NAME. Chronic treatment with losartan did not change
the protein expression of Mas and AT2 receptor and ACE (angiotensin-converting enzyme) and ACE2 in coronary
arteries from CoA rats, but induced a slight increase in AT2 receptor in aorta of these animals. Ang-(1–7)-induced
relaxation in aortas from sham-operated rats was absent in aortas from CoA rats. In vitro pre-treatment with
losartan restored the Ang-(1–7)-induced relaxation in aortic rings of CoA rats, which was blocked by the Mas
antagonist A-779 and L-NAME. These data demonstrate that Mas is strongly involved in coronary vasodilation and
that AT1 receptor (angiotensin II type 1 receptor) blockade potentiates the vasodilatory effects of Ang-(1–7) in the
coronary beds of pressure-overloaded rat hearts through NO-related AT2- and Mas-receptor-dependent mechanisms.
These data suggest the association of Ang-(1–7) and AT1 receptor antagonists as a potential therapeutic avenue for
coronary artery diseases.
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Palavras-chave
Angiotensin-(1–7), Mas receptor, Angiotensin II type 1 receptor (AT1 receptor), coronary vasodilation, Hypertrophic heart
Citação
SOUZA, Álvaro P. S. et al. Angiotensin II type 1 receptor blockade restores angiotensin-(1–7)-induced coronary vasodilation in hypertrophic rat hearts. Clinical Science, London, v. 125, n. 9, p. 449-459, 2013.