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RhoA activation contributes to sex differences in vascular contractions
Journal article   Open access   Peer reviewed

RhoA activation contributes to sex differences in vascular contractions

Daniel W Nuno, Victoria P Korovkina, Sarah K England and Kathryn G Lamping
Arteriosclerosis, thrombosis, and vascular biology, Vol.27(9), pp.1934-1940
09/2007
DOI: 10.1161/ATVBAHA.107.144675
PMID: 17556652
url
https://doi.org/10.1161/ATVBAHA.107.144675View
Published (Version of record) Open Access

Abstract

Studies have suggested that sex differences in endothelial function in part account for the lower incidence of cardiovascular disease in premenopausal women compared with men. Less is known about the role of smooth muscle. We hypothesized that signaling mechanisms that regulate calcium sensitivity in vascular muscle also play a role in determining sex differences in contractile function. In aorta, concentration-dependent contractions to serotonin were greater in male versus female mice whereas contractions to KCl and U46619 were similar. Nitric oxide or other endothelial-derived factors did not account for the difference in responses to serotonin because inhibition of nitric oxide synthase (NOS) with N(G)-nitro-L-arginine, genetic deficiency of endothelial NOS, and removal of endothelium increased contractions but did not abolish the enhanced contractions in aorta from males. Contractions in aorta from both males and females were abolished by a serotonergic 5HT2A receptor antagonist (ketanserin), however there was no sex difference in 5HT2A receptor expression. Activation of RhoA and Rho-kinase by serotonin was greater in aorta from males compared with females, but this was not related to greater expression of RhoA or Rho-kinase isoforms (ROCK1 and ROCK2). The sex difference in aortic contractions to serotonin was abolished by an inhibitor of Rho-kinase, Y27632. We conclude that increased contractions to serotonin in aorta from male mice are attributable to differences in RhoA/Rho-kinase activation in smooth muscle independent of differences in the expression of RhoA or Rho-kinase.
 Serotonin - physiology Protein-Serine-Threonine Kinases - physiology Calcium Signaling - physiology Nitric Oxide Synthase Type III Male rhoA GTP-Binding Protein - physiology Animals Muscle Contraction - physiology rho-Associated Kinases Sex Factors Female Mice Intracellular Signaling Peptides and Proteins - physiology Aorta - physiology Muscle, Smooth, Vascular - physiology Nitric Oxide Synthase Type II - metabolism

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