Acute intermittent hypercapnic hypoxia and sympathetic neurovascular transduction in men

Abstract

Key points summary Intermittent hypoxia leads to long-lasting increases in muscle sympathetic nerve activity and blood pressure contributing to increased risk for hypertension in obstructive sleep apnoea patients. We determined whether augmented vascular responses to increasing sympathetic vasomotor outflow, termed sympathetic neurovascular transduction (sNVT), accompanied changes in blood pressure following acute intermittent hypercapnic hypoxia (IH) in men. Lower body negative pressure was utilized to induce a range of sympathetic vasoconstrictor firing while measuring beat-by-beat blood pressure and forearm vascular conductance. IH reduced vascular shear stress and steepened the relationship between diastolic blood pressure and sympathetic discharge frequency suggesting greater systemic sNVT. Our results indicate that recurring cycles of acute IH characteristic of obstructive sleep apnoea could promote hypertension by increasing sNVT. Abstract Acute intermittent hypercapnic hypoxia (IH) induces long-lasting elevations in sympathetic vasomotor outflow and blood pressure in healthy humans. It is unknown whether IH alters sympathetic neurovascular transduction (sNVT), measured as the relationship between sympathetic vasomotor outflow and either forearm vascular conductance (FVC; regional sNVT) or diastolic blood pressure (DBP; systemic sNVT). We tested the hypothesis that IH augments sNVT by exposing healthy males to 40 consecutive 1-minute breathing cycles, each comprising 40-seconds of hypercapnic hypoxia (PETCO2: +4 ± 3 mm Hg above baseline; PETO2: 48 ± 3 mm Hg) and 20-seconds of normoxia (n = 9), or a 40-minute air-breathing control (n = 7). Before and after the intervention, lower body negative pressure (LBNP; 3 minutes at -15, -30, and -45 mmHg) was applied to elicit reflex increases in muscle sympathetic nerve activity (MSNA, fibular microneurography) while clamping end-tidal gases at baseline levels. Ventilation, arterial pressure (SBP, DBP, MAP), brachial artery blood flow (Q̇BA), FVC (Q̇BA/MAP), and MSNA burst frequency were measured continuously. Following IH, but not control, ventilation (5 l/min; 95% CI: 1 - 9), and MAP (5 mmHg; 95% CI: 1 - 9) were increased, while FVC (-0.2 ml/min/mm Hg; 95% CI: -0.0 - -0.4) and mean shear rate (SR; -21.9 /s; 95% CI: -5.8 - -38.0; all P < 0.05) were reduced. Systemic sNVT was increased following IH (0.25 mm Hg/burst/min; 95% CI: 0.01 – 0.49; P < 0.05), while changes in regional forearm sNVT were similar between IH and sham. Reductions in vessel wall shear stress and consequently nitric oxide production, may contribute to heightened systemic sNVT and provide a potential neuro-vascular mechanism for elevated blood pressure in obstructive sleep apnoea. This article is protected by copyright. All rights reserved