Acute intermittent hypercapnic hypoxia and sympathetic neurovascular transduction in men.

KEY POINTS: 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 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 intermittent hypercapnic hypoxia 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 (systemic sNVT). We tested the hypothesis that IH augments sNVT by exposing healthy males to 40 consecutive 1 min breathing cycles, each comprising 40 s of hypercapnic hypoxia ( P ETC O 2 : +4 ± 3 mmHg above baseline; P ET O 2 : 48 ± 3 mmHg) and 20 s of normoxia (n = 9), or a 40 min air-breathing control (n = 7). Before and after the intervention, lower body negative pressure (LBNP; 3 min at -15, -30 and -45 mmHg) was applied to elicit reflex increases in muscle sympathetic nerve activity (MSNA, fibular microneurography) when clamping end-tidal gases at baseline levels. Ventilation, arterial pressure [systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP)], brachial artery blood flow ( Q ̇ BA ), FVC ( Q ̇ BA /MAP) and MSNA burst frequency were measured continuously. Following IH, but not control, ventilation [5 L min-1 ; 95% confidence interval (CI) = 1-9] and MAP (5 mmHg; 95% CI = 1-9) were increased, whereas FVC (-0.2 mL min-1  mmHg-1 ; 95% CI = -0.0 to -0.4) and mean shear rate (-21.9 s-1 ; 95% CI = -5.8 to -38.0; all P < 0.05) were reduced. Systemic sNVT was increased following IH (0.25 mmHg burst-1  min-1 ; 95% CI = 0.01-0.49; P < 0.05), whereas 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 neurovascular mechanism for elevated blood pressure in obstructive sleep apnoea.