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Neurofibromatosis 1 (NF1) is an autosomal dominant disorder with complete penetrance and an estimated prevalence of 1 in 3000. Clinical manifestations are extremely variable. The disease is characterized by multiple café-au-lait spots (skin pigmentation), iris harmartomas, and multiple benign and malignant nerve sheath tumors (neurofibromas) in the central and peripheral nervous systems (Jett and Friedman 2010). NF1 vasculopathy is a serious and well documented but poorly understood feature of NF1. NF1 vasculopathy may result in hypertension, cerebrovascular disease, ischemia, aneurysm, hemorrhage or death in young adults (Rasmussen et al 2001). The response to standard therapeutic interventions is often disappointing (Friedman et al 2002), so further understanding of the underlying mechanisms for vascular complications in NF1 is essential. Endothelial and vascular smooth muscle functions are altered in Nf1+/- mice in vitro (Li et al 2001, Li et al 2006, Munchhof et al 2006), however, it is unknown how these alterations affect function of the vessel. We have compared vascular function of the thoracic aorta in Nf1+/- mice with age-matched control littermates (n=16) using a small vessel myograph (A/S Danish Myotechnology, Aarthus N, Denmark). Isometric force measurements revealed increased contraction in response to depolarization (maximal response of 3.3 ± 0.32 in Nf1+/- aorta versus 2.0 ± 0.22 in controls; p= 0.005), but diminished contraction in response to phenylephrine in Nf1+/- thoracic aorta at 6 months of age (pEC50 = 5.36 ± 0.18 in Nf1+/- aorta versus 7.02 ± 0.09 in controls; maximal response, Emax = 67.28 ± 3.4 in Nf1+/- aorta versus 86.34 ± 5.7; p= 0.008). Stress-strain curves indicated that arterial stiffness was increased at 6 months of age in Nf1+/-vessels. Elastin staining revealed disorganization of elastic fibers in Nf1+/- vessels. In conclusion, the pathogenesis of NF1 vasculopathy in the thoracic aorta increases stiffness and impairs vasomotor function. [ABSTRACT FROM AUTHOR]