title: Adrenomedullin inhibits angiotensin II-induced contraction in human aortic smooth muscle cells.
abstract: The vasodilating peptide adrenomedullin (AM) has been reported to regulate vascular tone as well as proliferation and differentiation of various cell types in an autocrine/paracrine manner. Our study was designed to investigate the effect of AM on Ang II-induced contraction on human aortic smooth muscle cells (HASMC) in vitro, evaluating the signal pathways involved. Our findings indicate that AM was able to inhibit HASMC Ang II-induced contraction (IC50 19 nM). AM stimulated cAMP production in a dose-dependent fashion as well. SQ 22.536, an adenylate cyclase inhibitor, and KT5720, a PKA inhibitor, blunted the AM effect, suggesting that it was mediated by the activation of the cAMP transduction pathway. Our results suggest that AM plays a role in the regulation of HASMC contraction by antagonizing the Ang II effects and may be involved in conditions of altered regulation of the blood vessels.
authors.affiliation: Dipartimento di Fisiopatologia Medica, V Clinica Medica, Policlinico Umberto I, Università La Sapienza Facoltà di Medicina, Viale del Policlinico, 00161 Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Rossi
authors.forename: Catia
authors.initials: C
authors.lastname: Zappa
authors.forename: Antonella
authors.initials: A
authors.lastname: Ferraresi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Santiemma
mesh_terms: D053607:Adrenomedullin; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D010455:Peptides; D014665:Vasodilator Agents; D000804:Angiotensin II; D053607:Adrenomedullin