A. Parenti et al., ANG II potentiates mitogenic effect of norepinephrine in vascular muscle cells: role of FGF-2, AM J P-HEAR, 280(1), 2001, pp. H99-H107
Citations number
36
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
We examined the possible cooperation between norepinephrine (NE) and ANG II
on proliferation of cultured vascular smooth muscle cells (VSMCs) and the
involved cellular mechanisms. Nanomolar NE concentrations stimulated VSMC p
roliferation through a prazosin-sensitive effect. The pretreatment of cells
with 100 nM ANG II for 24 h significantly potentiated the NE-induced VSMC
proliferation; this potentiating effect of ANG II was blocked by losartan b
ut was unaffected by the AT(2) receptor antagonist PD-123177. ANG II pretre
atment also potentiated the increase in inositol phosphate turnover and upr
egulated the cell expression of fibroblast growth factor (FGF-2) induced by
NE. Anti-FGF-2 neutralizing antibodies prevented the potentiating effect o
f ANG II on NE-induced cell growth. Both ANG II and NE stimulated extracell
ular signal-related kinase (ERK1) activation, but an ANG II potentiation of
the effect of NE on ERK1 activity was not detectable. Moreover, ANG II sig
nificantly increased protein synthesis but did not potentiate the hypertrop
hic effect of NE. These findings demonstrate that ANG II and NE cooperate i
n promoting VSMC growth and that FGF-2 upregulation is involved in this eff
ect.