Consequences of peripheral chemoreflex inhibition with low-dose dopamine in humans

Abstract

Low-dose dopamine inhibits peripheral chemoreceptors and attenuates the hypoxic ventilatory response (HVR) in humans. However, it is unknown: (1) whether it also modulates the haemodynamic reactions to acute hypoxia, (2) whether it also modulates cardiac baroreflex sensitivity (BRS) and (3) if there is any effect of dopamine withdrawal. We performed a double-blind, placebo-controlled study on 11 healthy male volunteers. At sea level over 2 days every subject was administered low-dose dopamine (2 μg kg(-1) min(-1)) or saline infusion, during which we assessed both ventilatory and haemodynamic responses to acute hypoxia. Separately, we evaluated effects of initiation and withdrawal of each infusion and BRS. The initiation of dopamine infusion did not affect minute ventilation (MV) or mean blood pressure (MAP), but increased both heart rate (HR) and cardiac output. Concomitantly, it decreased systemic vascular resistance. Dopamine blunted the ventilatory, MAP and HR reactions (hypertension, tachycardia) to acute hypoxia. Dopamine attenuated cardiac BRS to falling blood pressure. Dopamine withdrawal evoked an increase in MV. The magnitude of the increment in MV due to dopamine withdrawal correlated with the size of the HVR and depended on the duration of dopamine administration. The ventilatory reaction to dopamine withdrawal constitutes a novel index of peripheral chemoreceptor function.

Figures

Figure 1

A, baseline recording before infusion; B, recording during infusion; C, baseline prior to infusion withdrawal; D, recording after infusion withdrawal.

Figure 2

Open columns, saline infusion initiation; shaded columns, dopamine infusion initiation. *P < 0.05.

Figure 3

A, effects of dopamine infusion withdrawal on ventilatory parameters. B, example showing the effects of dopamine and placebo withdrawal on MV. C, an increase in MV after dopamine withdrawal presented as individual data. D, correlation between an increase in MV after dopamine withdrawal and hypoxic ventilatory response (HVR). *P < 0.05.

Figure 4

Example of the raw data showing the ventilatory and haemodynamic responses to hypoxia during (A) saline and (B) dopamine infusion.

Figure 5

Influence of dopamine on the ventilatory (A) and haemodynamic (B and C) responses to hypoxia. *P < 0.05