Role of arterial chemoreceptors in mediating the effects of endogenous adenosine on sympathetic nerve activity

Abstract

Background: Exogenous adenosine has been shown to increase muscle sympathetic nerve activity (MSNA), blood pressure, heart rate, and ventilation in conscious humans, effects attributed to peripheral chemoreceptor activation.

Methods and results: To determine whether endogenous adenosine has similar effects and whether they are mediated through chemoreceptor activation, we examined the effects of dipyridamole, an inhibitor of adenosine reuptake, on sympathetic nerve activity and ventilation. Twenty studies were conducted on separate days in 15 healthy volunteers. We examined responses to dipyridamole 0.56 mg/kg during room air breathing (n = 7), during hyperoxia (100% O2, n = 6), and during room air breathing after pretreatment with aminophylline (n = 7). During room air breathing, dipyridamole increased MSNA from 231 +/- 42 to 504 +/- 136 U/min, heart rate from 65 +/- 3.8 to 96 +/- 4.7 beats per minute, and systolic blood pressure from 129 +/- 3.5 to 140 +/- 4.8 mm Hg; central venous pressure decreased from 5.5 +/- 0.4 to 4.5 +/- 0.3 mm Hg (P < .01), and minute ventilation increased from 7.8 +/- 0.6 to 9.1 +/- 0.5 L/min (P < .01). During peripheral chemoreceptor suppression (with hyperoxia), there was a dissociation of the effects of dipyridamole on ventilation and sympathoexcitation. Effects on ventilation were attenuated, but sympathoexcitatory effects were not. Pretreatment with aminophylline, an adenosine receptor antagonist, either abolished (blood pressure, minute ventilation, and end-tidal CO2) or markedly attenuated (MSNA and heart rate) the effects of dipyridamole during room air breathing.

Conclusions: Augmentation of endogenous adenosine with dipyridamole increases sympathetic nerve activity and ventilation in conscious humans. The ventilatory effects of endogenous adenosine are mediated predominantly by chemoreceptor activation, but the sympathetic and hemodynamic responses to endogenous adenosine are probably mediated by an additional afferent mechanism that is independent of peripheral chemoreceptor activation.