Angiotensin II stimulates DNA and protein synthesis and increases cell size in human pulmonary artery smooth muscle cells via the AT1 receptor and MAPK activation.
Does Angiotensin II stimulate growth and MAPK activation in human pulmonary artery smooth muscle cells via AT1 receptors?
Angiotensin II promotes hypertrophy and protein/DNA synthesis in human pulmonary artery smooth muscle cells via the AT1 receptor and MAPK pathway, indicating a potential mechanism for pulmonary vascular remodeling.
To determine a potential role for the renin-angiotensin system in the growth of human pulmonary artery (PA) smooth muscle, we studied the localization of angiotensin (ANG) II-receptor subtypes by autoradiography in sections of human PA and in cultured PA smooth muscle cells (PASMCs) and examined the growth responses to ANG II in vitro. Specific 125I-labeled Sar1,Ile8ANG II binding was demonstrated within the pulmonary arterial media, but binding to cultured cells varied between isolates. Binding in tissues and cells was inhibited by the ANG II type 1 (AT1) receptor antagonist losartan but not by the type 2 (AT2) receptor antagonist PD-123319. Microautoradiographic studies indicated that cultured PASMCs exhibit heterogeneity with regard to ANG II binding sites. Addition of ANG II to serum-deprived PASMCs, exhibiting a relatively high level of 125I-Sar1,Ile8ANG II binding, led to a dose-dependent stimulation of DNA synthesis at 24 h and protein synthesis at 48 h. ANG II led to an increase in cell size without an increase in cell number. These effects were inhibited by losartan but not by PD-123319. In addition, ANG II led to rapid activation of mitogen-activated protein kinase (MAPK), and ANG II-stimulated DNA synthesis was inhibited by the specific inhibitor of MAPK PD-98059. We conclude that the AT1 receptor is expressed by human PASMCs in vivo and in vitro and is coupled to activation of MAPK and increased DNA and protein synthesis in vitro. These results are consistent with the hypothesis that ANG II may be involved in human pulmonary vascular remodeling.
Morrell et al. (Wed,) conducted a other in Pulmonary vascular remodeling. Angiotensin II vs. Losartan, PD-123319, PD-98059 (inhibitors) was evaluated on DNA synthesis, protein synthesis, and cell size. Angiotensin II stimulates DNA and protein synthesis and increases cell size in human pulmonary artery smooth muscle cells via the AT1 receptor and MAPK activation.
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