RESEARCH ARTICLE Src Family Kinases (SFK) Mediate Angiotensin

Angiotensin (Ang) II is the major bioactive peptide of the renin–angiotensin system (RAS); it contributes to the pathogenesis of hypertension by inducing vascular contraction and ad-verse remodeling, thus elevated peripheral resistance. Ang II also activates Src family ki-nases (SFK) in the vascular system, which has been implicated in cell proliferation and migration. However, the role of SFK in Ang II-induced hypertension is largely unknown. In this study, we found that administration of a SFK inhibitor SU6656 markedly lowered the level of systemic BP in Ang II-treated mice, which was associated with an attenuated phos-phorylation of the smooth-muscle myosin-light-chain (MLC) in the mesenteric resistant ar-teries. In the cultured human coronary artery smooth muscle cells (SMCs), pretreatment with SU6656 blocked Ang II-induced MLC phosphorylation and contraction. These results for the first time demonstrate that SFK directly regulate vascular contractile machinery to in-fluence BP. Thus our study provides an additional mechanistic link between Ang II and va-soconstriction via SFK-enhanced MLC phosphorylation in SMCs, and suggests that targeted inhibition of Src may provide a new therapeutic opportunity in the treatment of hypertension