Role of Nitric Oxide in Cardiovascular Disorders - Applications of Biotechnology in Cardiovascular Therapeutics - page 88

model (Kumar et al. 2008 ). Sodium nitrite significantly restored ischemic hind
limb blood flow in a time-dependent manner, with low-dose sodium nitrite being
most effective. Nitrite therapy significantly increased ischemic limb vascular den-
sity and stimulated endothelial cell proliferation. The effects of sodium nitrite
therapy were evident within 3 days of the ischemic insult demonstrating the
potency and efficacy of this therapy. Sodium nitrite therapy also increased isch-
emic tissue nitrite and NO metabolites compared to nonischemic limbs. Use of the
NO scavenger carboxy PTIO completely abolished sodium nitrite-dependent isch-
emic tissue blood flow and angiogenic activity consistent with nitrite reduction to
NO being the proangiogenic mechanism. These data demonstrate that chronic
sodium nitrite therapy is an effective therapy for peripheral artery disease and criti-
cal limb ischemia.
NO-Based Therapies for Raynaud's Phenomenon
Raynaud's phenomenon (RP) is characterized by transient reduction in blood supply
through the small arteries in the hands and feet. RP is a cutaneous microvascular
disorder whose pathophysiology appears to relate to disorders of local and/or reflex
thermoregulatory control of the skin circulation. Severe RP can cause digital necro-
sis. It has been hypothesized that NO may have a role in RP. Oral L-arginine has
been reported to reverse digital necrosis in RP suggesting that a defect in NOS
metabolism is present in Raynaud's phenomenon. Thus there is a potential role for
oral L-arginine therapy in Raynaud's phenomenon, especially in RP with digital
necrosis.
Nitrates are often prescribed for the treatment of RP, but currently available
formulations are limited by side effects, particularly headaches and dizziness.
Symptoms improve by application of glyceryl trinitrate ointment. A novel formula-
tion of topical nitroglycerin, MQX-503, was well tolerated and more effective than
placebo for the treatment of RP in a randomized clinical trial (Chung et al. 2009 ).
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