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  • Angiotensin-(1–7)-dependent vasorelaxation of the renal artery exhibits unique angiotensin and bradykinin receptor selectivity
  • Add time:08/07/2019         Source:sciencedirect.com

    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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