Reduced blood pressure responsiveness to skeletal muscle metaboreflex activation in older adults following inorganic nitrate supplementation

Abstract

The vasoactive molecule nitric oxide (NO) contributes to regulation of blood pressure (BP) at rest and during exercise. Age-related exaggerated increased BP responses during exercise have been proposed to be due in part to a decreased NO bioavailability and possibly an enhanced skeletal muscle metaboreflex. In the present study we sought to determine if age-related differences in BP responses to skeletal muscle metaboreflex activation exist. Additionally, since NO bioavailability can be improved with exogenous nitrate (NO₃^-) via the nitrate-nitrite-NO pathway, we tested the hypothesis that inorganic NO₃^- supplementation would reduce BP responses to muscle metaboreflex activation in healthy older adults. 13 older adults (67 ± 1 years) participated in a randomized, double-blind, placebo controlled crossover study consisting of four weeks of NO₃^- supplementation [beetroot powder; 250 mg (∼4.03 mmol) of NO₃^- and 20 mg (∼0.29 mmol) of NO₂^-] and four weeks of placebo (beetroot powder devoid of NO₃^-/NO₂^-). Skeletal muscle metaboreflex testing consisted of isometric handgrip exercise (IHG) at 30% of maximal voluntary contraction immediately followed by post exercise forearm ischemia (PEI), which was achieved by inflation of a rapid pressure cuff (240 mmHg) around the upper arm. BP responses were analyzed as the change (Δ) from baseline to the end of IHG and PEI. An additional 10 young adults (25 ± 1 years) were recruited to serve as a reference cohort and address if BP responses to skeletal muscle metaboreflex activation were greater with aging. BP responses to IHG were similar between the young and older adults. However, older adults demonstrated a greater increase in systolic BP during PEI (P < 0.05). Plasma NO₃^- and NO₂^-were increased following NO₃^- supplementation in older adults (P < 0.01). ΔSystolic BP (19 ± 2 vs. 13±3 mmHg, P < 0.05), ΔDiastolic BP (7 ± 1 vs. 5±1 mmHg, P < 0.05) and ΔMean arterial pressure (11 ± 1 vs. 8±2 mmHg, P < 0.05) were reduced during PEI following four weeks of NO₃^-supplementation, whereas placebo had no effect on ΔSystolic BP (16 ± 2 vs. 17±2 mmHg), ΔDiastolic BP (5 ± 1 vs. 7±1 mmHg), and ΔMean arterial pressure (8 ± 1 vs. 10±1 mmHg) during PEI (all P > 0.05). These data suggest that inorganic NO₃^- supplementation attenuates skeletal muscle metaboreflex mediated increases in BP during exercise in older adults.

Keywords: Aging; Blood pressure responsiveness; Inorganic nitrate; Metaboreflex; Nitric oxide.