Abstract

Percutaneously absorbed carbon dioxide enhances blood flow. The mechanism by which it does so is unclear, but we hypothesized that it involves bicarbonate ions. BALB/c mice were bathed in neutral bicarbonate ionized water (NBIW) and showed increased blood bicarbonate levels and blood flow via phosphorylation of peripheral vascular endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO). Phosphorylation of eNOS and NO production were also increased in human umbilical vein endothelial cells cultured in medium containing NBIW, and NBIW showed reactive oxygen species scavenging activity. In a double-blind, randomized study in men and women aged 30 to 59 years with subjective cold intolerance, bathing in NBIW elevated body temperature faster than bathing in a control solution and improved chills and sleep quality. Taken together, our results show that percutaneously absorbed carbon dioxide changes to bicarbonate ions, which act directly on endothelial cells to increase NO production by phosphorylation of eNOS and thus improve blood flow.

Highlights

  • Mice bathed in sodium bicarbonate water (SBW; n = 5) showed nonsignificant changes compared with control mice (p = 0.244) (Fig. 1a)

  • Western blotting analysis showed a significant increase in the amount of endothelial nitric oxide synthase (eNOS) in the vascular tissue in both the neutral bicarbonate ionized water (NBIW) and SBW groups compared with the control group (NBIW: n = 5, p = 0.039*, SBW: n = 5, p = 0.041*; control: n = 6) (Fig. 1d,e)

  • The phospho-eNOS level tended to be higher in both the NBIW and SBW groups than in the control group, whereby the effect size was greater in the NBIW group (NBIW: p = 0.075, Hedge’s g = 0.95 [95% CI: − 0.299 to 2.205]; SBW: p = 0.281, Hedge’s g = 0.36, 95% CI [− 0.833 to 1.56]) (Fig. 1f)

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Summary

Introduction

BALB/c mice were bathed in neutral bicarbonate ionized water (NBIW) and showed increased blood bicarbonate levels and blood flow via phosphorylation of peripheral vascular endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO). Our results show that percutaneously absorbed carbon dioxide changes to bicarbonate ions, which act directly on endothelial cells to increase NO production by phosphorylation of eNOS and improve blood flow. The mechanism by which percutaneously absorbed ­CO2 enhances blood flow was previously thought to be attributable to the Bohr e­ ffect[17], in which the absorbed C­ O2 increases C­ O2 pressure at subcutaneous capillaries, causing ­O2 to be released from hemoglobin. Many aspects of the actual mechanism remain to be elucidated

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