Central Adenosine Receptors Differentially Contribute To The Nicotine‐Induced Attenuation Of Reflex Tachycardic Responses To Baroreceptor Unloading

Abstract

Nicotine impairs reflex cardiac sympathoexcitatory responses to baroreceptor unloading. The role of central adenosine receptors in the nicotine-baroreflex interaction was investigated. Baroreflex curves relating reflex heart rate (HR) responses to decreases in blood pressure (BP) evoked by i.v. doses (1–16 μg/kg) of sodium nitroprusside (SNP) was constructed in conscious male rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRSSNP). Whether administered i.v. (25 or 100 μg/kg) or intracis-ternally (2 or 5 μg/rat), nicotine caused dose-dependent downward shifts in SNP curves and reductions in BRSSNP. BRSSNP was also reduced in rats treated intracisternally with 8-phenyltheophylline (8-PT, nonselective adenosine receptor antagonist), 8-(3-Chlorostyryl) caffeine (CSC, A2A antagonist), or VUF5574 (A3 antagonist) in contrast to no effect for DPCPX (A1 antagonist), alloxazine (A2B antagonist), or dipyridamole (adenosine uptake inhibitor). Pretreatment with 8-PT or CSC abrogated the BRSSNP depressant effect of nicotine whereas other adenosine receptor antagonists were without effect. It is concluded that central pathways of A2A or A3 receptors tonically facilitate reflex cardiac sympathoexcitation. Further, disruption of central A2A receptor signaling mediates the nicotine-baroreflex interaction. Supported by Faculty of Pharmacy, Alexandria University, Egypt.