Abstract

Vascular endothelial dysfunction develops with aging as a result of insufficient nitric oxide (NO) bioavailability. Supplementation with nitrite, a precursor to NO, may improve NO bioavailability. We tested the safety, dose (80 vs. 160 mg/d), duration (4 and 10 weeks), and efficacy of oral sodium nitrite for improving endothelial dysfunction in middle‐aged and older (MA/O) adults (n=28, 61±1 yr) in a randomized, placebo‐controlled, double‐blind pilot intervention study. Both doses of nitrite acutely increased plasma nitrite (10 to 20‐fold, p<0.05) and were well‐tolerated without symptomatic hypotension or clinically‐relevant elevations in blood methemoglobin (maximal value=1.2%). Ten weeks of nitrite capsules chronically increased plasma nitrite (p<0.05, both doses) without altering blood pressure. Endothelial function, measured by brachial artery flow‐mediated dilation (FMD), was increased 55‐65% vs. baseline (p<0.05) after 10, but not 4 weeks of nitrite vs. placebo. The reduction in FMD with 20 min of forearm cuff occlusion (ischemia‐reperfusion [I/R] stress) was only half as great (‐50%, p<0.05) after nitrite treatment vs. placebo (‐100%). These results indicate that sodium nitrite supplementation for 10 weeks at 80 or 160 mg/d is well‐tolerated, improves vascular endothelial function, and provides protection from endothelial I/R injury in MA/O adults.Grant Funding Source: Supported by NIH HL107105, RR025780, AG000279

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