Human studies use varying levels of low-dose (1-4 μg·kg(-1)·min(-1)) dopamine to examine peripheral chemosensitivity, based on its known ability to blunt carotid body responsiveness to hypoxia. However, the effect of dopamine on the ventilatory responses to hypoxia is highly variable between individuals. Thus we sought to determine 1) the dose response relationship between dopamine and peripheral chemosensitivity as assessed by the ventilatory response to hypoxia in a cohort of healthy adults, and 2) potential confounding cardiovascular responses at variable low doses of dopamine. Young, healthy adults (n = 30, age = 32 ± 1, 24 male/6 female) were given intravenous (iv) saline and a range of iv dopamine doses (1-4 μg·kg(-1)·min(-1)) prior to and throughout five hypoxic ventilatory response (HVR) tests. Subjects initially received iv saline, and after each HVR the dopamine infusion rate was increased by 1 μg·kg(-1)·min(-1). Tidal volume, respiratory rate, heart rate, blood pressure, and oxygen saturation were continuously measured. Dopamine significantly reduced HVR at all doses (P < 0.05). When subjects were divided into high (n = 13) and low (n = 17) baseline chemosensitivity, dopamine infusion (when assessed by dose) reduced HVR in the high group only (P < 0.01), with no effect of dopamine on HVR in the low group (P > 0.05). Dopamine infusion also resulted in a reduction in blood pressure (3 μg·kg(-1)·min(-1)) and total peripheral resistance (1-4 μg·kg(-1)·min(-1)), driven primarily by subjects with low baseline chemosensitivity. In conclusion, we did not find a single dose of dopamine that elicited a nadir HVR in all subjects. Additionally, potential confounding cardiovascular responses occur with dopamine infusion, which may limit its usage.

Hypoglycemia results in a reduction in cardiac baroreflex sensitivity and a shift in the baroreflex working range to higher heart rates. This effect is mediated in part by the carotid chemoreceptors. Therefore, we hypothesized hypoglycemia-mediated changes in baroreflex control of heart rate would be blunted in carotid body resected patients when compared with healthy controls. Five patients with bilateral carotid body resection for glomus tumors and ten healthy controls completed a 180-minute hyperinsulinemic, hypoglycemic (~3.3 mmol.L−1) clamp. Changes in heart rate, blood pressure, and spontaneous cardiac baroreflex sensitivity were assessed. Baseline baroreflex sensitivity was not different between groups (p>0.05). Hypoglycemia resulted in a reduction in baroreflex sensitivity in both groups (Main effect of time, p<0.01) and responses were lower in resected patients when compared with controls (Main effect of group, p<0.05). Hypoglycemia resulted in large reductions in systolic (−17±7 mmHg) and mean (−14±5 mmHg) blood pressure in resected patients that were not observed in controls (Interaction of group and time, p<0.05). Despite lower blood pressures, increases in heart rate with hypoglycemia were blunted in resected patients (Interaction of group and time, p<0.01). Major novel findings from this study demonstrate that intact carotid chemoreceptors are essential for increasing heart rate and maintaining arterial blood pressure during hypoglycemia in humans. These data support a contribution of the carotid chemoreceptors to blood pressure control and highlight the potential widespread effects of carotid body resection in humans.

The purpose of the present investigation was to examine the contribution of the carotid body chemoreceptors to changes in baroreflex control of heart rate with exposure to hypoxia. We hypothesized spontaneous cardiac baroreflex sensitivity (scBRS) would be reduced with hypoxia and this effect would be blunted when carotid chemoreceptor activity was reduced with low‐dose dopamine. Fifteen healthy adults (11 M/4 F) completed two visits randomized to intravenous dopamine or placebo (saline). On each visit, subjects were exposed to 5‐min normoxia (~99% SpO2), followed by 5‐min hypoxia (~84% SpO2). Blood pressure (intra‐arterial catheter) and heart rate (ECG) were measured continuously and scBRS was assessed by spectrum and sequence methodologies. scBRS was reduced with hypoxia (P < 0.01). Using the spectrum analysis approach, the fall in scBRS with hypoxia was attenuated with infusion of low‐dose dopamine (P < 0.01). The decrease in baroreflex sensitivity to rising pressures (scBRS “up‐up”) was also attenuated with low‐dose dopamine (P < 0.05). However, dopamine did not attenuate the decrease in baroreflex sensitivity to falling pressures (scBRS “down‐down”; P > 0.05). Present findings are consistent with a reduction in scBRS with systemic hypoxia. Furthermore, we show this effect is partially mediated by the carotid body chemoreceptors, given the fall in scBRS is attenuated when activity of the chemoreceptors is reduced with low‐dose dopamine. However, the improvement in scBRS with dopamine appears to be specific to rising blood pressures. These results may have important implications for impairments in baroreflex function common in disease states of acute and/or chronic hypoxemia, as well as the experimental use of dopamine to assess such changes.

Objective: Given recent evidence from rodents supporting a novel role for the carotid bodies in insulin‐mediated sympathoexcitation, we sought to determine whether carotid chemoreceptor desensitization would reduce muscle sympathetic nerve activity (MSNA) during hyperinsulinemia in humans. Methods: Young, healthy subjects (n=4, 30±2 yrs) breathed hyperoxic gas (End‐tidal O2 = 100%, PaO2 505±13 mmHg) for 15 min at baseline and during steady‐state hyperinsulinemia (5±1 vs 53±1 µU/mL). Hyperinsulinemia was achieved using a 90‐min hyperinsulinemic (1 mU/kg FFM/min), euglycemic (108±4 mg/dL) clamp. CO2 was maintained at resting levels (PaCO2 41±1 mmHg). Changes in heart rate, blood pressure, minute ventilation, and MSNA (microneurography of the peroneal nerve) were assessed. Results: Hyperinsulinemia increased MSNA [burst frequency (p<0.01), burst incidence (p=0.02), total activity (p=0.02)]. Hyperoxia decreased heart rate (p=0.01) and minute ventilation (p=0.11), and increased mean blood pressure (p=0.04). Consistent with our hypothesis, the effect of hyperoxia on MSNA (Δ) was different between baseline and hyperinsulinemia (burst frequency, p=0.03; burst incidence, p=0.10). Conclusion: These data are the first to suggest the carotid chemoreceptors may contribute to insulin‐mediated sympathoexcitation in humans. Grant Funding Source: Supported by: NIH R01 DK090541 (MJJ), NIH T32 DK07352 (JKL)