Angiotensin-(1-7)-dependent vasorelaxation of the renal artery exhibits unique angiotensin and bradykinin receptor selectivity

作者：Yousif Mariam H M; Benter Ibrahim F; Diz Debra I; Chappell Mark C^*

来源：Peptides, 2017, 90: 10-16.

DOI：10.1016/j.peptides.2017.02.001

• Angiotensin
• Kidney
• Renal artery
• Endothelium
• c-GMP

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-AT(1) 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 x 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 AT(7)/Mas receptor (MasR) [D-Pro(7)]-Ang-(1-7) and ID-Ala(7)]-Ang-(1-7) significantly reduced the maximal response to 12 +/- 1% and 18 +/- 3%, respectively. Surprisingly, the AT(2)R receptor antagonist PD123319, the AT(1) R 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 AT(7)/Mas, AT(1), AT(2) and B-2 receptor subtypes.

• 出版日期2017-4