title: Src Family Kinases (SFK) Mediate Angiotensin II-Induced Myosin Light Chain Phosphorylation and Hypertension.
abstract: 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 adverse remodeling, thus elevated peripheral resistance. Ang II also activates Src family kinases (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 phosphorylation of the smooth-muscle myosin-light-chain (MLC) in the mesenteric resistant arteries. 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 influence BP. Thus our study provides an additional mechanistic link between Ang II and vasoconstriction 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.
authors.affiliation: Weinberg College of Arts and Sciences, Northwestern University, Chicago, IL, United States of America.
authors.forename: Bo
authors.initials: B
authors.lastname: Qin
authors.affiliation: Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America.
authors.forename: Junlan
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018994:Myosin Light Chains; D000804:Angiotensin II; D019061:src-Family Kinases