Dose dependent effects of nitrate supplementation on cardiovascular control and microvascular oxygenation dynamics in healthy rats

Abstract

High dose nitrate (NO3−) supplementation via beetroot juice (BR, 1 mmol/kg/day) lowers mean arterial blood pressure (MAP) and improves skeletal muscle blood flow and O2 delivery/utilization matching thereby raising microvascular O2 pressure (PO2mv). We tested the hypothesis that a low dose of NO3− supplementation, consistent with a diet containing NO3− rich vegetables (BRLD, 0.3 mmol/kg/day), would be sufficient to cause these effects. Male Sprague–Dawley rats were administered a low dose of NO3− (0.3 mmol/kg/day; n = 12), a high dose (1 mmol/kg/day; BRHD, n = 6) or tap water (control, n = 10) for 5 days. MAP, heart rate (HR), blood flow (radiolabeled microspheres) and vascular conductance (VC) were measured during submaximal treadmill exercise (20 m/min, 5% grade, equivalent to ∼60% of maximal O2 uptake). Subsequently, PO2mv (phosphorescence quenching) was measured at rest and during 180 s of electrically-induced twitch contractions (1 Hz, ∼6 V) of the surgically-exposed spinotrapezius muscle. BRLD and BRHD lowered resting (control: 139 ± 4, BRLD: 124 ± 5, BRHD: 128 ± 9 mmHg, P 0.05), each of which increased significantly for the BRHD condition (all P mean response time, MRT; control: 16.6 ± 2.1, BRHD: 23.3 ± 4.7 s) following the onset of contractions compared to control, in the BRLD group this effect did not reach statistical significance (BRLD: 20.9 ± 1.9 s, P = 0.14). These data demonstrate that while low dose NO3− supplementation lowers MAP during exercise it does so in the absence of augmented muscle blood flow, VC and PO2mv; all of which are elevated at a higher dose. Thus, in healthy animals, a high dose of NO3− supplementation seems necessary to elicit significant changes in exercising skeletal muscle O2 delivery/utilization