The effect of acute oral pyridoxine supplementation on peripheral chemoreflex sensitivity in human hypertension
Authors: Babbage Thalia , Fan Jui-Lin , Sayegh Ana , Dawes Matt , Paton Julian , Fisher James 
Published: May 2023

ATP has been identified as an important signalling molecule in the carotid body. Animal models of hypertension have uncovered that ATP transmission via purinergic (P2) receptors increases carotid body tonicity and sensitivity, which drives sympathetic outflow and elevates blood pressure. A naturally occurring metabolite of pyridoxine (Vitamin B6), namely pyridoxal-5-phosphate, is a non-selective P2X receptor antagonist. In this study we tested the hypothesis that oral administration of pyridoxine reduces peripheral chemoreflex sensitivity and blood pressure in human hypertension. 14 treated hypertensive patients (4 men, 71±5 yr, 27±6 kg·m-2, 156±19/83±8 mmHg) completed a double-blind placebo-controlled crossover study with either oral pyridoxine (600 mg) or placebo. Two-hours later, minute ventilation (V̇E), end-tidal partial pressures of oxygen and carbon dioxide (PETO2 and PETCO2), mean arterial pressure (MAP), and heart rate (HR) were recorded during an isocapnic hypoxic rebreathing protocol (target PETO2 45mmHg). Cardiorespiratory responses were taken as the change from baseline to peak rebreathing (final 15s). Arterial oxygen saturation (SaO2) was calculated from PETO2 using the Severinghaus equation, and peripheral chemoreflex sensitivity taken as ΔV̇E divided by ΔSaO2. Baseline V̇E(13.02±3.26 vs. 12.68±4.13 L·min-1, P=0.616), MAP (109±11 vs. 104±10 mmHg, P=0.058), and HR (63±11 vs. 62±8 BPM, P=0.463), were not different between pyridoxine and placebo conditions, respectively. The ΔV̇E response to isocapnic hypoxia tended to be blunted with pyridoxine compared to placebo (6.88±3.94 vs. 9.87±7.69 L·min-1; P=0.188), but this did not reach statistical significance. Similarly, peripheral chemoreflex sensitivity was not different with pyridoxine compared to placebo (-0.46±0.31 vs. -0.64±0.49 L·min-1·%-1, P=0.148). However, individuals with a higher peripheral chemoreflex sensitivity in the placebo condition, displayed a more marked reduction in peripheral chemoreflex sensitivity following pyridoxine (R2=0.63, P=0.005). While HR and MAP increased during isocapnic hypoxia (both P<0.001), the magnitude of this response did not differ with pyridoxine or placebo administration. In this preliminary study, oral pyridoxine lowered neither blood pressure nor peripheral chemoreflex sensitivity in human hypertension. However, oral pyridoxine did lower peripheral chemoreflex sensitivity in those hypertension patients in whom baseline peripheral chemoreflex sensitivity (i.e., placebo condition) was highest. It is possible that oral pyridoxine supplementation may be beneficial for those hypertensive patients who exhibit overactivation of their peripheral chemoreflex. Health Research Council of New Zealand (Ref# 19/687), the University of Auckland Faculty Research Development Fund, and the New Zealand Lottery Grants Board (R-LHR-2021-153114). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.