Role of the carotid body chemoreceptors in baroreflex control of blood pressure during hypoglycaemia in humans

Abstract

Activation of the carotid body chemoreceptors with hypoxia alters baroreceptor-mediated responses. We aimed to examine whether this relationship can be translated to other chemoreceptor stimuli (i.e. hypoglycaemia) by testing the following hypotheses: (i) activation of the carotid body chemoreceptors with hypoglycaemia would reduce spontaneous cardiac baroreflex sensitivity (sCBRS) in healthy humans; and (ii) desensitization of the carotid chemoreceptors with hyperoxia would restore sCBRS to baseline levels during hypoglycaemia. Ten young healthy adults completed two 180 min hyperinsulinaemic [2 mU (kg fat-free mass)(-1) min(-1)], hypoglycaemic (∼ 3.2 μmol ml(-1)) clamps, separated by at least 1 week and randomized to normoxia (arterial partial pressure of O2, 122 ± 10 mmHg) or hyperoxia (arterial partial pressure of O2, 424 ± 123 mmHg; to blunt activation of the carotid body glomus cells). Changes in heart rate, blood pressure, plasma catecholamines, heart rate variability (HRV) and sCBRS were assessed. During hypoglycaemia, HRV and sCBRS were reduced (P < 0.05) and the baroreflex working range was shifted to higher heart rates. When hyperoxia was superimposed on hypoglycaemia, there was a greater reduction in blood pressure and a blunted rise in heart rate when compared with normoxic conditions (P < 0.05); however, there was no detectable effect of hyperoxia on sCBRS or HRV during hypoglycaemia (P > 0.05). In summary, hypoglycaemia-mediated changes in HRV and sCBRS cannot be attributed exclusively to the carotid chemoreceptors; however, the chemoreceptors appear to play a role in resetting the baroreflex working range during hypoglycaemia.

Figure 1

Heart rate and blood pressure responses to hyperinsulinaemic-hypoglycaemia under normoxic and hyperoxic conditions. Change from baseline (Mean±SEM). A. Heart rate, B. Systolic blood pressure, C. Diastolic blood pressure, D. Mean blood pressure. When hyperoxia was superimposed on hypoglycaemia there was a greater reduction in blood pressure and a blunted rise in heart rate when compared to normoxic conditions

Figure 2

Spontaneous cardiac baroreflex sensitivity (sCBRS) during hyperinsulinaemichypoglycaemia under normoxic and hyperoxic conditions. (Mean±SEM) A. Absolute measures of baroreflex sensitivity (relationship between R-R interval and systolic blood pressure). B. Absolute measures of baroreflex sensitivity (relationship between heart rate and systolic blood pressure). sCBRS tended to be reduced from baseline during hypoglycaemia and there was no detectable effect of hyperoxia.

Figure 3

Spontaneous cardiac baroreflex sensitivity during hyperinsulinaemichypoglycaemia under normoxic and hyperoxic conditions. Group average regressions between heart rate and systolic blood pressure are presented with operating points (Mean±SEM). Baseline sCBRS measures were not different between visits (p=0.26) and were thus averaged. sCBRS was significantly reduced from baseline during hypoglycemia and the baroreflex working range was shifted to higher heart rates. Hyperoxia did not alter sCBRS, however the baroreflex working range was shifted back toward baseline levels.

Figure 4

Heart rate variability at baseline and during hyperinsulinaemic-hypoglycaemia under normoxic and hyperoxic conditions (Mean and Individual data points). A. Mean NN Interval (time between normal cardiac cycles, reported in ms). B. Low Frequency normalized [reported in normalized units (nu)]. C. High Frequency normalized [reported in normalized units (nu)]. D. Low Frequency/High Frequency ratio. Although reductions in HRV with hypoglycaemia were not reversed with hyperoxia, this was primarily driven by the response from a single individual. When this subject was removed from the analysis, hyperoxia tended to attenuate any effect of hypoglycaemia on HRV (Mean NN Interval, p=0.08) including a reversal of the effects on cardiovagal tone (High Frequency, p=0.12) and sympathovagal balance (LF/HF, p=0.10).