کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5514798 | 1541689 | 2017 | 7 صفحه PDF | دانلود رایگان |
- Ang-(1-7) potently relaxes the rat renal artery with an ED50 of 3.4 nM.
- Vasorelaxant effects of Ang-(1-7) are blocked the AT7/Mas receptor antagonists D-Ala7-Ang-(1-7) (A779) and D-Pro7-Ang-(1-7).
- Vasorelaxant actions of Ang-(1-7) are also attenuated by the AT1 receptor antagonist losartan and the AT2 receptor antagonist PD123319.
- Bradykinin B2 receptor antagonist HOE140 blocks Ang-(1-7)-dependent relaxation suggesting that Ang-(1-7) may stimulate the local release of bradykinin.
Angiotensin-(1-7) [Ang-(1-7)] exhibits blood pressure lowering actions, inhibits cell growth, and reduces tissue inflammation and fibrosis which may functionally antagonize an activated Ang II-AT1 receptor axis. Since the vascular actions of Ang-(1-7) and the associated receptor/signaling pathways vary in different vascular beds, the current study established the vasorelaxant properties of the heptapeptide in the renal artery of male Wistar male rats. Ang-(1-7) produced an endothelium-dependent vasodilator relaxation of isolated renal artery segments pre-contracted by a sub-maximal concentration of phenylephrine (PE) (3 Ã 10â7 M). Ang-(1-7) induced vasodilation of the rat renal artery with an ED50 of 3 ± 1 nM and a maximal response of 42 ± 5% (N = 10). The two antagonists (10â5 M each) for the AT7/Mas receptor (MasR) [D-Pro7]-Ang-(1-7) and [D-Ala7]-Ang-(1-7) significantly reduced the maximal response to 12 ± 1% and 18 ± 3%, respectively. Surprisingly, the AT2R receptor antagonist PD123319, the AT1R antagonist losartan and B2R antagonist HOE140 (10â6 M each) also significantly reduced Ang-(1-7)-induced relaxation to 12 ± 2%, 22 ± 3% and 14 ± 7%, respectively. Removal of the endothelium or addition of the soluble guanylate cyclase (sGC) inhibitor ODQ (10â5 M) essentially abolished the vasorelaxant response to Ang-(1-7) (10 ± 4% and 10 ± 2%, P < 0.05). Finally, the NOS inhibitor LNAME (10â4 M) reduced the response to 13 ± 2% (p < 0.05), but the cyclooxygenase inhibitor indomethacin failed to block the Ang-(1-7) response. We conclude that Ang-(1-7) exhibits potent vasorelaxant actions in the isolated renal artery that are dependent on an intact endothelium and the apparent stimulation of a NO-sGC pathway. Moreover, Ang-(1-7)-dependent vasorelaxation was sensitive to antagonists against the AT7/Mas, AT1, AT2 and B2 receptor subtypes.
Journal: Peptides - Volume 90, April 2017, Pages 10-16