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Dietary sodium nitrate supplementation restores blood flow regulation in Becker muscular dystrophy (1165.1)
Author(s) -
Nelson Michael,
Rader Florian,
Tang Xiu,
Stabler Thomas,
Allen Jason,
Victor Ronald
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1165.1
Subject(s) - vasoconstriction , nitric oxide , medicine , endocrinology , blood flow , sodium nitrate , reflex , mdx mouse , chemistry , blood pressure , vascular smooth muscle , muscular dystrophy , sodium nitroprusside , sodium , dystrophin , organic chemistry , smooth muscle
Chronic administration of a nitric oxide‐donating drug fully corrects abnormal blood flow regulation in the mdx mouse model of dystrophinopathy. As a first step to clinical translation, we treated 6 men with Becker muscular dystrophy with a single oral dose of sodium nitrate‐ a simple, exogenous inorganic nitric oxide donor. We measured reflex vasoconstriction (ΔHb02, near infrared spectroscopy; evoked by lower body negative pressure) at rest and during rhythmic handgrip exercise, before and 3 hours after ~8.4 mmol of oral sodium nitrate. Before treatment, blood flow regulation was impaired in BMD, because handgrip exercise caused no attenuation of reflex vasoconstriction (ΔHbO2:‐17±2 vs. ‐16±2 %, rest vs. HG). Remarkably, sodium nitrate supplementation more than doubled plasma nitrate and nitrite levels, and restored exercise‐induced attenuation of reflex vasoconstriction (ΔHbO2: ‐18±1 vs. ‐11±2; P <.001, rest vs. HG). Moreover, the exercise‐induced increase in forearm muscle blood flow, as measured by Doppler ultrasound, nearly tripled after sodium nitrate supplementation (Δ from baseline: 102 + 19% before treatment compared to 271 + 39 % after treatment), despite having no effect on basal flow. Taken together, these data indicate that oral sodium nitrate can recapitulate the normal regulation of blood flow in exercising dystrophic skeletal muscle, which is normally achieved by sarcolemmal nNOS.