Role of the carotid chemoreceptors in insulin-mediated sympathoexcitation in humans

Abstract

We examined the contribution of the carotid chemoreceptors to insulin-mediated increases in muscle sympathetic nerve activity (MSNA) in healthy humans. We hypothesized that reductions in carotid chemoreceptor activity would attenuate the sympathoexcitatory response to hyperinsulinemia. Young, healthy adults (9 male/9 female, 28 ± 1 yr, 24 ± 1 kg/m²) completed a 30-min euglycemic baseline followed by a 90-min hyperinsulinemic (1 mU·kg fat-free mass^-1·min^-1), euglycemic infusion. MSNA (microneurography of the peroneal nerve) was continuously measured. The role of the carotid chemoreceptors was assessed at baseline and during hyperinsulinemia via 1) acute hyperoxia, 2) low-dose dopamine (1-4 µg·kg^-1·min^-1), and 3) acute hyperoxia + low-dose dopamine. MSNA burst frequency increased from baseline during hyperinsulinemia (P < 0.01). Acute hyperoxia had no effect on MSNA burst frequency at rest (P = 0.74) or during hyperinsulinemia (P = 0.83). The insulin-mediated increase in MSNA burst frequency (P = 0.02) was unaffected by low-dose dopamine (P = 0.60). When combined with low-dose dopamine, acute hyperoxia had no effect on MSNA burst frequency at rest (P = 0.17) or during hyperinsulinemia (P = 0.85). Carotid chemoreceptor desensitization in young, healthy men and women does not attenuate the sympathoexcitatory response to hyperinsulinemia. Our data suggest that the carotid chemoreceptors do not contribute to acute insulin-mediated increases in MSNA in young, healthy adults.

Keywords: carotid body; hyperinsulinemia; muscle sympathetic nerve activity.

Fig. 1.

Study timeline. All subjects completed 30 min of resting baseline followed by a 90-min hyperinsulinemic, euglycemic infusion. Steady-state measures were collected at baseline and during the last 30 min of the insulin infusion. At this time, subjects breathed room air freely for 15 min and then were acutely exposed to hyperoxia. An initial group of subjects (protocol 1) completed a saline visit only. A second group of individuals (protocol 2) participated in 2 identical study visits randomized to placebo (saline) or intravenous dopamine. Dopamine/saline was infused for 15 min before collection of baseline measurements until the end of the 90-min insulin infusion. FFM, fat-free mass.

Fig. 2.

Representative data traces. Subjects breathed room air (21% O₂, normoxia) and then quietly switched to 100% O₂ to experimentally “turn off” the carotid chemoreceptors. Because of the acute effects of hyperoxia on the carotid chemoreceptors, data were analyzed from the first 1 min of hyperoxia exposure and compared with data from the first min of normoxia immediately preceding the exposure. MSNA, muscle sympathetic nerve activity; au, arbitrary units.

Fig. 3.

Effect of acute hyperoxia on muscle sympathetic nerve activity at baseline and during hyperinsulinemia. Individual (● and ○) and mean (open and shaded bars) values from 13 subjects are shown. A and B: average of 1 min before hyperoxia and during the first 1 min of hyperoxia for burst frequency and burst incidence. Data were analyzed by 2-way repeated-measures ANOVA and pairwise multiple comparison (Student-Newman-Keuls method).

Fig. 4.

Effect of low-dose dopamine at baseline and during hyperinsulinemia. Individual (● and ○) and mean (open and shaded bars) values from 7 subjects are shown. A and B: muscle sympathetic nerve activity burst frequency and burst incidence from an average of 5 min during quiet normoxic breathing before saline/dopamine infusion (preinfusion), during steady-state saline/dopamine infusion at baseline (baseline), and during steady-state hyperinsulinemia (hyperinsulinemia). Data were analyzed by 2-way repeated-measures ANOVA and pairwise multiple comparison (Student-Newman-Keuls method).

Fig. 5.

Effect of acute hyperoxia and low-dose dopamine at baseline and during hyperinsulinemia. Individual (● and ○) and mean (open and shaded bars) values from 8 subjects are shown. A and B: muscle sympathetic nerve activity burst frequency and burst incidence before dopamine infusion (preinfusion), during steady-state dopamine infusion at baseline (baseline), and during steady-state hyperinsulinemia (hyperinsulinemia). Data are reported as an average of 1 min before and during hyperoxia. Data were analyzed by 2-way repeated-measures ANOVA.