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Angiotensin‐(1–7) opposes agonist‐induced constriction in endothelium denuded rat aortic rings via NO and PI3‐Kinase pathways
Author(s) -
Allahdadi Kyan James,
Leite Romulo,
Webb R. Clinton,
Santos Robson A. S.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1206.3
Subject(s) - phenylephrine , agonist , vasodilation , chemistry , vasoconstriction , angiotensin ii , endothelium , nitric oxide , medicine , endocrinology , constriction , nitric oxide synthase , pharmacology , receptor , blood pressure
Background: Angiotensin‐(1–7) [Ang‐(1–7)] is a potent vasodilator eliciting its effects primarily through endothelial derived factors. However, a direct effect of Ang‐(1–7) on the vascular smooth muscle (VSM) has not been fully investigated. This study tested the ability of Ang‐(1–7) to regulate agonist‐mediated VSM constriction in the absence of the endothelium. Methods and Results: Endothelium denuded thoracic aortic rings (3 mm) from male Wistar rats (250–300g) were used in this study. Pretreatment with Ang‐(1–7) (10 −5 M) significantly attenuated both Ang II and phenylephrine (PE) concentration response curves (10 −10 –10 −6 M). This attenuated constrictor response was abolished by incubation with the selective Ang‐(1–7) receptor antagonist, A779 (10 −5 M), the non‐selective nitric oxide synthase (NOS) inhibitor, L‐NAME (10 −4 M), or the phosphatidylenositol 3‐kinase (PI3Kinase) inhibitor, LY29004 (10 −5 M). Conclusion: Our data suggest that Ang‐(1–7) activates its receptor and signals through NO derived from NOS isoforms within VSM. Additionally, we provided evidence that this opposed vasoconstrictor response involves the PI3‐kinase pathway. We suggest that this endothelium independent Ang‐(1–7)‐induced attenuation of the agonist‐mediated constriction of the VSM is an important mechanism by which Ang‐(1–7) participates in vascular reactivity and consequently blood pressure regulation.