Dietary nitrate supplementation attenuates the mechanoflex in older women with early menopause: A pilot study

Kazumasa Manabe, Jeung Ki Yoo, Ryosuke Takeda, Bryon Curtis, Monique Roberts-Reeves, Qi Fu

Research output: Contribution to journalArticlepeer-review


Women who reached early menopause (EM, 40-44 yrs) have a greater risk for cardiovascular disease than women with normal menopause (NM, 50-54 yrs), which may be attributed to a longer duration of estrogen loss and a greater reduction in nitric oxide bioavailability in both the peripherals and center. Previous studies have shown that dietary nitrate supplementation improves cardiovascular function in older women, but how autonomic neural control changes in daily living, such as during exercise, has been involved is unclear. We examined the hypothesis that 2wks continuous use of dietary nitrate supplements would attenuate the exercise pressor reflex in older women with EM. Six EM (65±4 [SD] yrs) and 8 NM (64±2 yrs) women participated in this randomized, placebo-controlled, double-blind, cross-over pilot study. All subjects underwent 2 wks of beetroot juice (BRJ; 140 ml containing ~800 mg nitrate per day) or placebo (140 ml nitrate-depleted BRJ, daily) intervention with ≥14 days of wash-out. Before and after each intervention period, subjects performed SHG using the dominant hand at 40% of maximum voluntary contraction (MVC) until fatigue, followed by 2 min of PECA with an upper arm cuff inflated to 250 mmHg. Heart rate (HR; ECG), blood pressure (BP; finger photoplethysmography), muscle sympathetic nerve activity (MSNA; microneurography), and respiration (capnography) were continuously measured. In addition, 24-h ambulatory BP standard deviation (SD) was monitored before and after each intervention (an indication of BP variability). There were no differences in baseline HR, BP and MSNA, MVC, and the time to fatigue between the EM and NM groups before and after intervention (all p>0.05). At the first 30 s of SHG, the EM group showed significant decreases in MSNA burst frequency (DBF; -4.5±6.5 in EM vs. 2.5±6.2 bursts/min in NM, p=0.065) and burst incidence (DBI; -10.6±12.6 vs. 2.6±8.4 bursts/100 heartbeats, p=0.037) after BRJ intervention compared with the NM group (Figure1A and B). However, there were no differences between groups at fatiguing exercise and during PECA after the intervention. The interventional changes in 24-h diastolic BP SD had a positive correlation with ΔMSNA BF (r=0.55, p=0.053) and BI (r=0.58, p=0.036) at the first 30 s of SHG in all subjects and EM individuals were in the left-lower area (Figure2 A and B). These results suggest that dietary nitrate supplementation may attenuate and mechanoreflex, but not the metaboreflex, in older women with EM during static hand grip, which has a relation with BP variability during ambulation. Certainly, these preliminary observations need to be verified in more older women in future studies.

Original languageEnglish (US)
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
StatePublished - May 1 2022
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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