Endothelial responses of the aorta from adrenomedullin transgenic mice and knockout mice

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Abstract

Adrenomedullin (AM) is a potent vascular wall-derived vasorelaxing peptide which induces the release of nitric oxide (NO). To explore the role of endogenous AM in vascular function, we examined the effects of acetylcholine (ACh), AM, and AM receptor antagonists [AM (22-52), and calcitonin gene-related peptide (CGRP) (8-37)] on the isometric tension of aortic rings isolated from AM transgenic (TG) and knockout (KO) mice and wild type littermatesc (WT). ACh and AM caused a dose-dependent reduction of the isometric tension of aortic rings, but the degree of vasodilatation was smaller in TG than in KO or WT (%Δtension [10-6 mol/l ACh]: KO -69±10%, WT -39±8%, TG -29±1%, p<0.01). On the other hand, NG-nitro-L-arginine methyl ester, an NO synthase inhibitor, induced greater vasoconstriction in TG (%Δtension 10-5mol/l: KO +78±16%, WT +99±27%, TG +184±20%, p<0.01), whereas E-4021, a cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase inhibitor, caused greater vasodilation in TG mice. Both AM antagonists increased tension in TG to a greater extent than in KO or WT mice (%Δtension [10-6 mol/l CGRP (8-37)]: KO +24±5%, WT +51±6%, TG +75±7%, p<0.01). Endothelial denudation of the aorta diminished the vasoconstriction caused by the AM antagonists. In conclusion, the amounts of AM expressed in the aortic endothelium influenced baseline NO release. AM antagonists increased vascular tone in WT as well as in TG, suggesting that endogenous AM plays a physiological role in the regulation of aortic tone.

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Nishimatsu, H., Hirata, Y., Shindo, T., Kurihara, H., Suzuki, E., Sata, M., … Nagai, R. (2003). Endothelial responses of the aorta from adrenomedullin transgenic mice and knockout mice. Hypertension Research, 26(SUPPL.). https://doi.org/10.1291/hypres.26.S79

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