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Rho/Rho‐kinase Mediate Gender Differences in Vascular Contractions
Author(s) -
Lamping Kathryn Griffin,
Korovkina Victoria P,
England Sarah K,
Nuno Daniel W
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a520-b
Subject(s) - rho associated protein kinase , rhoa , endocrinology , medicine , rock2 , serotonin , rock1 , vasoconstriction , contractility , receptor , contraction (grammar) , activator (genetics) , biology , kinase , signal transduction , microbiology and biotechnology
Objective: Premenopausal women have a reduced risk for vascular disease compared to men, however, the underlying mechanism is unknown. We hypothesized that gender differences in vascular contractility are mediated by differential activation of the Rho/rho‐kinase pathway. Methods and results: In isolated aortic rings, dose‐dependent contractions to serotonin were greater in male versus female mice. Greater contractions in male arteries compared to female arteries persisted following inhibition of NOS with nitro‐L‐arginine, genetic deficiency of eNOS, and removal of endothelium indicating that NO and/or other endothelial‐derived factors do not account for the difference. Inhibition of serotonin 5HT2A receptors and rho‐kinase (Y27632) abolished the difference in serotonin‐induced contractions. The greater contraction in males following serotonin was not due to enhanced expression of 5HT2A receptors, rho‐kinase isoforms (ROCK1 or ROCK2), RhoA, the upstream activator of rho‐kinase or CPI‐17 (western immunoblotting). However, modified ELISA analyses demonstrated a greater basal activity and serotonin‐induced activation of Rho in male aorta versus female aorta. Conclusion: We conclude that differences in RhoA activation underlie the gender influences in contractions to serotonin.