ROLE OF ARTERIAL CHEMORECEPTORS IN MEDIATING THE EFFECTS OF ENDOGENOUS ADENOSINE ON SYMPATHETIC-NERVE ACTIVITY

Background Exogenous adenosine has been shown to increase muscle sympa thetic nerve activity (MSNA), blood pressure, heart rate, and ventilat ion in conscious humans, effects attributed to peripheral chemorecepto r activation. Methods and Results To determine whether endogenous aden osine has similar effects and whether they are mediated through chemor eceptor activation, we examined the effects of dipyridamole, an inhibi tor of adenosine reuptake, on sympathetic nerve activity and ventilati on. Twenty studies were conducted on separate days in 15 healthy volun teers. We examined responses to dipyridamole 0.56 mg/kg during room ai r breathing (n=7), during hyperoxia (100% O-2, n=6), and during room a ir 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 syst olic 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 minu te ventilation increased from 7.8+/-0.6 to 9.1+/-0.5 L/min (P<.01). Du ring peripheral chemoreceptor suppression (with hyperoxia), there was a dissociation of the effects of dipyridamole on ventilation and sympa thoexcitation. Effects on ventilation were attenuated, but sympathoexc itatory effects were not. Pretreatment with aminophylline, an adenosin e receptor antagonist, either abolished (blood pressure, minute ventil ation, and end-tidal CO2) or markedly attenuated (MSNA and heart rate) the effects of dipyridamole during room air breathing. Conclusions Au gmentation of endogenous adenosine with dipyridamole increases sympath etic nerve activity and ventilation in conscious humans. The ventilato ry effects of endogenous adenosine are mediated predominantly by chemo receptor activation, but the sympathetic and hemodynamic responses to endogenous adenosine are probably mediated by an additional afferent m echanism that is independent of peripheral chemoreceptor activation.