Peripheral artery disease (PAD) is a manifestation of atherosclerosis that produces
progressive narrowing and occlusion of the arteries supplying the lower extremities. The most
common clinical manifestation of PAD is claudication, i.e., a severe functional limitation
identified as gait dysfunction and walking-induced leg muscle pain relieved by rest. The
standard therapies for claudication include the medications cilostazol and pentoxifylline,
supervised exercise therapy and operative revascularization. Recent data demonstrated that 24
weeks of treatment with the angiotensin-converting enzyme (ACE) inhibitor Ramipril produces
improvements in the walking performance of patients with claudication that are higher than
those of cilostazol and pentoxifylline and similar to those produced by supervised exercise
therapy and operative revascularization. The mechanisms by which Ramipril therapy produces
this impressive improvement in the functional capacity of claudicating patients remain
unknown. The Investigators hypothesize that treatment of claudicating PAD patients with
Ramipril will improve walking performance and quality of life by improving the myopathy of
the gastrocnemius. Improved myopathy is a consequence of reduced oxidative damage, reduced
TGF-β1 production by vascular smooth muscle cells and reduced collagen deposition in the
affected gastrocnemius.