Effects of simulated obstructive sleep apnoea on the human carotid baroreceptor-vascular resistance reflex

Abstract

Obstructive sleep apnoea (OSA), which is characterized by periodic inspiratory obstruction, is associated with hypertension and possibly with changes in the baroreceptor reflex. In this investigation we induced changes in inspiratory resistance and in inspiratory oxygen and carbon dioxide content, which simulate some of the changes in OSA, to determine whether this caused changes in the gain or setting of the carotid baroreflex. In eight healthy subjects (aged 21-62 years) we changed the stimulus to carotid baroreceptors, using neck chambers and graded pressures of -40 to +60 mmHg, and assessed vascular resistance responses in the brachial artery from changes in blood pressure (Finapres) divided by brachial artery blood flow velocity (Doppler ultrasound). Stimulus-response curves were defined during (a) sham (no additional stimulus), (b) addition of an inspiratory resistance (inspiratory pressure -10 mmHg), (c) breathing asphyxic gas (12% O(2), 5% CO(2)), and (d) combined resistance and asphyxia. Sigmoid or polynomial functions were applied to the curves and maximum differentials (equivalent to peak gain) and the corresponding carotid pressures (equivalent to 'set point') were determined. The sham test had no effect on either gain or 'set point'. Inspiratory resistance alone had no effect on blood pressure and did not displace the curve. However, it reduced gain from -3.0 +/- 0.6 to -2.1 +/- 0.4 units (P < 0.05). Asphyxia alone did increase blood pressure (+7.0 +/- 1.1 mmHg, P < 0.0005) and displaced the curve to higher pressures by +16.8 +/- 2.1 mmHg (P < 0.0005). However, it did not affect gain. The combination of resistance and asphyxia both reduced gain and displaced the curve to higher pressures. These results suggest that inspiratory resistance and asphyxia cause changes in the baroreceptor reflex which could lead to an increase in blood pressure. These changes, if sustained, could provide a mechanism linking hypertension to obstructive sleep apnoea.

Figure 1. A sample recording showing the application of negative neck chamber pressure (mmHg) and the responses of arterial blood pressure (mmHg) and brachial flow velocity (cm s⁻¹)

Respiratory cycles were taken from the P_ET,CO2 curve (mmHg). Control measurements were taken from the mean blood pressure and blood flow velocity during the two respiratory cycles preceding the onset of stimulation and vascular resistance was calculated as pressure/flow. Values of vascular resistance were calculated using values of mean blood pressure and blood flow velocity for each respiratory cycle during stimulation and calculated as a percentage change from control. The maximum change was taken as the response.

Figure 2. Example of the effects of breathing with an inspiratory resistance on the carotid baroreceptor pressure–response curve

Baseline values in absence of applied neck chamber pressure are taken as 100%. Note the reduction in slope with little displacement of the curve.

Figure 3. Example of the effects of asphyxia on the carotid baroreceptor pressure–response curve

Baseline values in absence of applied neck chamber pressure are taken as 100%. Note there is no change in slope of the curve, but the curve is displaced to the right.

Figure 4. Example of the effects of a combination of asphyxia and inspiratory resistance on the carotid baroreceptor pressure–response curve

Baseline values in absence of applied neck chamber pressure are taken as 100%. Note the reduction in slope of the curve and the curve is displaced to the right.

Figure 5. Carotid baroreflex sensitivity during control and test conditions

Asphyxia alone had no significant effect but inspiratory resistance either alone or in combination with asphyxia significantly reduced sensitivity.

Figure 6. Baroreflex ‘set point’ during control and test conditions

Inspiratory resistance had no significant effect on ‘set point’ but asphyxia, either alone or in combination with inspiratory resistance significantly increased ‘set point’.