Urotensin II is an autocrine/paracrine growth factor for aortic adventitia of rat

Urotensin II (UII) is a potent vasoconstrictive peptide; however, its significance in vascular adventitia has not been clearly elucidated. In this study, rat aortic adventitia showed mRNA expression and immunoreactivity of UII and its receptor (UT). Moreover, radioligand-binding assay showed that maximum binding capacity (Bmax) of [125I]-UII was higher in adventitia than in media (28.60 ± 1.94 vs. 20.21 ± 1.11 fmol/mg, P < 0.01), with no difference in binding affinity (dissociation constant [Kd] 4.27 ± 0.49 vs. 4.60 ± 0.40 nM, P > 0.05). Furthermore, in cultured adventitial fibroblasts, UII stimulated DNA synthesis, collagen synthesis and secretion in a concentration-dependent manner. These effects were inhibited by the UII receptor antagonist urantide (10− 6 mol/l), Ca2+ channel blocker nicardipine (10− 5 mol/l), protein kinase C inhibitor H7 (10− 6 mol/l), and mitogen-activated protein kinase inhibitor PD98059 (10− 6 mol/l) but not the phosphatidyl inositol-3 kinase inhibitor wortmannin (10− 7 mol/l). UII may act as an autocrine/paracrine factor through its receptor and the Ca2+ channel, protein kinase C, and mitogen-activated protein kinase signal transduction pathways, in the pathogenesis of vascular remodeling by activating vascular adventitia.