Background: It has been supposed that alterations in vascular smooth muscle function may play a role in the pathogenesis of dilated cardiomyopathy (DCM) in X-linked muscular dystrophies. Although mouse models for DCM exist, contractile properties of smooth muscle in these disorders have not been characterized yet. Methods: Isolated aortic smooth muscle preparations of dystrophin knockout mice (C57BL/mdx, 20–30 g, 14–20 weeks) were investigated and compared to age-matched wild-type muscles (C57BL/10). Isometric force of contraction and contraction/relaxation kinetics were measured under physiological conditions (37°C, [Ca2+]o 1.8 mM). Results: Aortic smooth muscle preparations of mdx mice generated about half of steady state force (Fss) compared with wild-type muscles (Fss: 0.13±0.07 vs 0.22±0.13 mN/mm2, p=0.028). Contraction kinetics were not significantly different between both muscle types (time to half peak: 25±3 vs 23±3 sec, p=ns). Following addition of verapamil to precontracted muscles, mdx mice showed significantly slower relaxation kinetics (time to half relaxation: 7.38±2.36 vs 4.34±1.23 min, p<0.001). Conclusions: Our results suggest that in a dystrophin-deficient mouse model with dilated cardiomyopathy, contractile dysfunction also occurs in vascular smooth muscle. Alterations in smooth muscle function could play a role in the pathogenesis of certain forms of hereditary dilated cardiomyopathies.