Increased Plasma Nitrite Enhances Exercise Performance in PAD:-A Nitric Oxide Effect?

Abstract

Peripheral Arterial Disease is the manifestation of a failure to adequately supply blood flow and O2 to working tissues and presents as claudication pain during walking which subsides with rest. Any intervention that can improve tissue perfusion during exercise in PAD subjects is clinically significant. Nitric oxide (NO) bioavailability is essential for vascular health and function and is implicated in aerobic exercise performance. Dietary inorganic nitrate is absorbed in the gut, converted to nitrite (NO2-) by comensural bacteria in saliva and then reabsorbed to become concentrated in the blood. Plasma NO2- is a marker of vascular NO production but recent findings suggest it may also be a protected circulating "sink" that can be converted to NO during hypoxic conditions, possibly aiding perfusion. PURPOSE: To determine the effects of a dietary provision of plasma nitrate on plasma NO2- and subsequent cardiopulmonary graded exercise test (CPX) performance in PAD subjects. METHODS: This was a randomized open label cross-over study of a HIGH (beet juice) versus a LOW (orange juice) nitrate drink (7 days between tests). On each visit subjects (n=8) underwent resting blood draws, followed by 500ml of juice and subsequent blood draws at 2hr, 3hr (pre-CPX), immediately and 10 minutes post CPX. Measures of brachial artery endothelial function following reactive hyperemia and calf tissue oxygenation using near-infra red spectroscopy during the CPX were also performed. All blood samples were immediately treated, snap frozen and stored for later analysis for plasma NO2- and nitrate using reductive chemiluminescence. RESULTS: There were no changes from rest (180±60nM) in plasma NO2- following the LOW drink. The HIGH drink increased plasma NO2- levels after 3 hours (1139nM±815, p≥0.01). Subjects walked 18% longer before reporting the onset of claudication pain (COT) (183±84sec to 215±99sec, p≥0.01) and 14% longer before stopping (TTE) (467± 223sec to 533±233sec, p≥0.01) following the HIGH vs LOW beverage. Interestingly, DBP was lower in the HIGH group at rest and during CPX testing (p≥0.05). CONCLUSION: A high nitrate drink increased plasma NO2- at 3 hours post consumption. This was associated with an increase in exercise performance (COT and TTE) in PAD subjects. Supported by Wake Forest TSC & Duke Pepper OAIC grants to JDA