Angiotensin-(1-7)-dependent vasorelaxation of the renal artery exhibits unique angiotensin and bradykinin receptor selectivity.
Angiotensin-(1-7)-dependent vasorelaxation of the renal artery exhibits unique angiotensin and bradykinin receptor selectivity.
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DOI：
10.1016/j.peptides.2017.02.001
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发表时间：
2017-04
期刊：
影响因子：
3
通讯作者：
Chappell MC
中科院分区：
文献类型：
--
作者：
Yousif MHM;Benter IF;Diz DI;Chappell MC
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 × 10−7 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 (10−5 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 (10−6 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 (10−5 M) essentially abolished the vasorelaxant response to Ang-(1–7) (10 ± 4% and 10 ± 2%, P < 0.05). Finally, the NOS inhibitor LNAME (10−4 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.
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影响因子：
5.8
作者：
Chappell MC
通讯作者：
Chappell MC
DOI：
10.1152/ajpheart.1995.269.1.h313
发表时间：
1995-07-01
影响因子：
4.8
作者：
BENTER, IF;FERRARIO, CM;DIZ, DI
通讯作者：
DIZ, DI
影响因子：
1.9
作者：
Bosnyak, S.;Widdop, R. E.;Jones, E. S.
通讯作者：
Jones, E. S.
影响因子：
20.1
作者：
Lautner, Roberto Queiroga;Villela, Daniel C.;Santos, Robson A. S.
通讯作者：
Santos, Robson A. S.
影响因子：
3
作者：
CHAPPELL, MC;JACOBSEN, DW;TALLANT, EA
通讯作者：
TALLANT, EA