Role of Nitric Oxide–cGMP Pathway in Adrenomedullin-Induced Vasodilation in the Rat

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Abstract
—We previously reported that adrenomedullin (AM), a potent vasodilator peptide discovered in pheochromocytoma cells, stimulates nitric oxide (NO) release in the rat kidney. To further investigate whether the NO-cGMP pathway is involved in the mechanisms of AM-induced vasodilation, we examined the effects of E-4021, a cGMP-specific phosphodiesterase inhibitor, on AM-induced vasorelaxation in aortic rings and perfused kidneys isolated from Wistar rats. We also measured NO release from the kidneys using a chemiluminescence assay. AM (10−10 to 10−7 mol/L) relaxed the aorta precontracted with phenylephrine in a dose-dependent manner. Denudation of endothelium (E) attenuated the vasodilatory action of AM (10−7 mol/L AM: intact (E+) −25.7±5.2% versus denuded (E−) −7.8±0.6%, P<0.05). On the other hand, pretreatment with 10−8 mol/L E-4021 augmented AM-induced vasorelaxation in the intact aorta (−49.0±7.9%, P<0.05) but not in the denuded one. E-4021 also enhanced acetylcholine (ACh)-induced vasorelaxation i...