Taylor, Jennifer L.

This study was performed to examine the role of the carotid bodies (CB) in glucoregulation during prolonged exercise in humans. Six healthy males (35 ± 5 yrs) completed two 120 minute bouts of cycling exercise (65% VO 2 max), during a dopamine infusion (D; 2 μg/kg/min) to acutely inactivate the CB, or a placebo, saline infusion (P). Arterial blood was drawn for glucose and counter‐regulatory hormones at baseline and during exercise (60–80: 60–80 minute mean; EE: end exercise). All variables at baseline were similar between conditions. Glucose concentration decreased throughout exercise and was similar between trials (60–80: 90 ± 7 vs. 98 ± 14; EE: 75 ± 12 vs. 80 ± 10 mg/dl; D vs. P respectively). However, when compared to baseline values, EE glucose had a greater decrease in 4 subjects during D, whereas 2 subjects had a greater attenuation during P. Glucagon was similar at 60–80 (108 ± 42 vs. 84 ± 40 pg/ml; D vs. P respectively), but was greater at EE in D than P (204 ± 104 vs. 136 ± 70 pg/ml). Cortisol (60–80: 13 ± 5 vs. 16 ± 4; EE: 22 ± 3 vs. 20 ± 7 μg/dl; D vs. P respectively) and growth hormone (60–80: 13 ± 3 vs. 12 ± 3; EE: 12 ± 4 vs. 10 ± 4 ng/ml; D vs. P respectively) concentrations were not different between conditions. Our preliminary results indicate that blood glucose during exercise with CB desensitization varies between subjects, and that the CB might contribute to blood glucose regulation during exercise. Funding: NIH R01DK090541

Cerebral vasodilator responses to hypercapnia decrease with aging, and recent data suggests sex differences in cerebrovascular regulation exist. Yet, it is unknown how sex and age interact in response to the stress of cyclooxygenase inhibition. We examined cerebral vasodilator responses to hypercapnia in 7 young men (YM), 8 young women (YW), 7 older men (OM), and 6 older women (OW) before (CON) and during cyclooxygenase (COX) inhibition via indomethacin (INDO). There was no age by sex interaction in middle cerebral artery velocity responses to hypercapnia (MCAv Slope). However, when accounting for mean arterial pressure during hypercapnia, there was an age by sex interaction in cerebrovascular conductance index (CVCi Slope). YM demonstrated higher CVCi Slope (1.27 ± 0.21 AU) compared with YW (0.65 ± 0.10 AU) and older adults (0.58 ± 0.10 AU in OM; 0.66 ± 0.06 AU in OW; p<0.05 for all). There was no difference in CVCi Slope between YW and OW, indicating that the age‐associated reduction in CVCi Slope only pertains to men. During INDO, there was an age by sex interaction for the ΔCVCi Slope (from CON to INDO) with YM having a greater slope compared with both YW (0.72 ± 0.15 vs. 0.27 ± 0.13 AU; p<0.01) and OM (0.26 ± 0.18 AU; p<0.01). Taken together, our results suggest that sex differences exist in the cerebrovascular response to hypercapnia with and without COX inhibition and that the effect of age is different in women compared to men.

Elevated central hemodynamics and arterial stiffness are associated with increased peripheral resistance and higher sympathetic nervous system activity. Additionally, consumption of a meal is known to be sympathoexcitatory. However, the acute effects of a meal on aortic wave reflection and stiffness are unknown. Therefore, we tested the hypothesis that aortic wave reflection and stiffness would increase following a meal. We examined these effects using high‐fidelity radial arterial pressure waveforms and carotid‐femoral pulse wave velocity (PWV), measured non‐invasively via applanation tonometry, before and 60 and 180 min after ingestion of a liquid mixed meal (Ensure, 40% of daily energy expenditure) in 15 healthy adults (25 ± 2 y; 8M/7F). Both peripheral and central pressures were reduced 180 min from baseline. Yet contrary to our hypothesis, augmentation index (15 ± 4 vs. 2 ± 3 vs. 8 ± 3%), augmentation index normalized for heart rate (9 ± 4 vs. −2 ± 3 vs. 3 ± 3%), augmented pressure (6 ± 2 vs. 1 ± 1 vs. 3 ± 1 mmHg) as well as carotid‐femoral PWV (7.3 ± 0.2 vs. 6.7 ± 0.2 vs. 6.7 ± 0.1 m/s) were substantially reduced at 60 and 180 min following the meal (P < 0.05 for all). Taken together, our results suggest that a liquid mixed meal acutely decreases central hemodynamics and arterial stiffness in healthy adults. NIH K23 DK82424 (TC) P30 DK50456 (MNOC) UL1 RR024150 (MCCTSA) HL105467 (DPC)

New Findings What is the central question of this study? Hyperoxia blunts hypoglycaemia counterregulation in healthy adults. We hypothesized that this effect is mediated by the carotid bodies and that: (i) hyperoxia would have no effect on hypoglycaemia counterregulation in carotid body‐resected patients; and (ii) carotid body‐resected patients would exhibit an impaired counterregulatory response to hypoglycaemia. What is the main finding and its importance? Our data indicate that the effect of hyperoxia on hypoglycaemic counterregulation is mediated by the carotid bodies. However, a relatively normal counterregulatory response to hypoglycaemia in carotid body‐resected patients highlights: (i) the potential for long‐term adaptations after carotid body resection; and (ii) the importance of redundant mechanisms in mediating hypoglycaemia counterregulation. Hyperoxia reduces hypoglycaemia counterregulation in healthy adults. We hypothesized that this effect is mediated by the carotid bodies and that: (i) hyperoxia would have no effect on hypoglycaemia counterregulation in patients with bilateral carotid body resection; and (ii) carotid body‐resected patients would exhibit an impaired counterregulatory response to hypoglycaemia. Five patients (three male and two female) with bilateral carotid body resection for glomus tumours underwent two 180 min hyperinsulinaemic, hypoglycaemic (∼3.3 mmol l−1) clamps separated by a minimum of 1 week and randomized to either normoxia (21% fractional inspired O2) or hyperoxia (100% fractional inspired O2). Ten healthy adults (seven male and three female) served as control subjects. Hypoglycaemia counterregulation in carotid body‐resected patients was not significantly altered by hyperoxia (area under the curve expressed as a percentage of the normoxic response: glucose infusion rate, 111 ± 10%; cortisol, 94 ± 6%; glucagon, 107 ± 7%; growth hormone, 92 ± 10%; adrenaline, 89 ± 26%; noradrenaline, 79 ± 15%; main effect of condition, P > 0.05). This is in contrast to previously published results from healthy adults. However, the counterregulatory responses to hypoglycaemia during normoxia were not impaired in carotid body‐resected patients when compared with control subjects (main effect of group, P > 0.05). Our data provide further corroborative evidence that the effect of hyperoxia on hypoglycaemic counterregulation is mediated by the carotid bodies. However, relatively normal counterregulatory responses to hypoglycaemia in carotid body‐resected patients highlight the importance of redundant mechanisms in mediating hypoglycaemia counterregulation.

New Findings What is the central question of this study? Activation of the carotid body chemoreceptors with hypoxia alters baroreceptor‐mediated responses in humans. We aimed to examine whether this relationship can be translated to other chemoreceptor stimuli (i.e. hypoglycaemia). What is the main finding and its importance? We show that hypoglycaemia‐mediated changes in heart rate variability and baroreflex sensitivity cannot be attributed exclusively to the carotid chemoreceptors; however, the chemoreceptors play a role in resetting the baroreflex working range during hypoglycaemia. These results provide a potential mechanism for impaired glycaemic control and increased risk of cardiac arrhythmias in patients with carotid chemoreceptor overactivity (i.e. sleep apnoea). 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.