Adrenomedullin inhibits angiotensin II-induced contraction in human aortic smooth muscle cells.
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.
Rossi
Fabio
F
Dipartimento di Fisiopatologia Medica, V Clinica Medica, Policlinico Umberto I, Università La Sapienza Facoltà di Medicina, Viale del Policlinico, 00161 Rome, Italy.
Zappa
Catia
C
Ferraresi
Antonella
A
Santiemma
Vittorio
V
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*
D010455:Peptides; D014665:Vasodilator Agents; D000804:Angiotensin II; D053607:Adrenomedullin