The Effects of Intermittent Hypoxia on the Vasculature and Carotid Baroreflex Regulation

Intermittent hypoxia (IH) occurs in association with obstructive sleep apnea and is thought to contribute to the pathogenesis of hypertension through mechanisms that include endothelial dysfunction, arterial stiffness, increased vascular resistance and impaired arterial baroreflex. The purpose of this study was to examine the acute effects of IH on the vasculature and carotid baroreflex to identify the early contributors to IH‐induced hypertension. We hypothesized that six hours of IH would increase mean arterial pressure (MAP), reduce endothelium‐dependent vasodilatation, impair vascular strain, induce oscillatory arterial shear patterns and shift the carotid baroreflex to operate at higher MAP while eliciting impaired control of leg vascular conductance (LVC). Healthy, young (26.3±1.3 years), normotensive (123±2.5 mmHg/65±1.6 mmHg) men (n=10) free of sleep apnea were exposed to two six hour conditions in randomized order: 1) IH [1‐min room air followed by 1‐min hypoxia (mean minimum oxygen saturation=80.7±0.4%; mean±SEM)], and 2) Sham IH (oxygen saturation=96.7±0.4%). Arterial blood pressure was recorded by using 24‐hour ambulatory blood pressure monitoring. Micro‐and macro‐vascular reactivity was measured by using reactive hyperemia flow‐mediated dilation before and immediately after each condition. During each exposure, vascular strain was measured by 2D speckle tracking in the common carotid and femoral artery (CCA and CFA), and hemodynamics were measured in the brachial artery and CFA using duplex ultrasound. Carotid baroreflex control of MAP and LVC was assessed following each condition by using the variable pressure neck chamber technique (target pressures: −80, −60, −40, −20, +20 and +40 mmHg). Intermittent hypoxia elevated 24‐hour MAP (2.6±0.8 mmHg, P =0.008) and tended to increase nocturnal systolic blood pressure (SBP, 3.9±1.8 mmHg, P =0.053). The augmented SBP may be caused by increased arterial stiffness and vascular resistance. Micro‐ and macro‐vascular reactivity were unaffected by IH but decreased by 17.5±5.5% and 14.1±4.7% following each testing day ( P <0.001, P =0.025) due to a blunted shear rate response. Vascular strain was reduced in the CCA during IH ( P =0.014) and a trend towards IH‐impaired CFA strain was observed ( P =0.055). Only the lower limb hemodynamics were affected by IH, exhibiting reduced blood flow (SHAM: 188.3±18.6 ml/min; IH: 158.0±1.6 ml/min, P =0.016) and increased oscillatory shear index by 20.3±5.7% ( P =0.036). Intermittent hypoxia displaced the carotid baroreflex control of MAP curve to higher arterial blood pressures ( P =0.045) and blunted LVC responses to hypertensive stimuli (−40 mmHg; SHAM: 24.0±2.5%, IH: 18.3±2.2%, P =0.044; −60 mmHg, SHAM: 31.8±3.2%; IH: 22.0±2.3%, P =0.003; −80 mmHg, SHAM: 40.6±3.9%, IH: 32.2±3.9%, P =0.002). In contrast to our hypotheses, we found that IH had no effect on micro‐ and macro‐vascular endothelial function. However, the differential impact of IH on upper and lower limb oscillatory shear patterns suggest endothelial function in the lower limb may be impaired before the upper limb. Impairments in vascular strain, lower limb hemodynamic shear patterns and carotid baroreflex control precede changes in upper arm endothelial function following six‐hours of IH and may be important in the early pathogenesis of IH‐induced hypertension. Support or Funding Information Natural Sciences and Engineering Research Council of Canada, Canada Foundation for Innovation