Role of adenosine A{sub 2A} receptor signaling in the nicotine-evoked attenuation of reflex cardiac sympathetic control

Journal Article · Mon Aug 01 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.04.014· OSTI ID:21587808

El-gowilly, Sahar M; Fouda, Mohamed A; Saad, Evan I

Baroreflex dysfunction contributes to increased cardiovascular risk in cigarette smokers. Given the importance of adenosinergic pathways in baroreflex control, the hypothesis was tested that defective central adenosinergic modulation of cardiac autonomic activity mediates the nicotine-baroreflex interaction. Baroreflex curves relating changes in heart rate (HR) to increases or decreases in blood pressure (BP) evoked by i.v. doses (1-16 {mu}g/kg) of phenylephrine (PE) and sodium nitroprusside (SNP), respectively, were constructed in conscious rats; slopes of the curves were taken as measures of baroreflex sensitivity (BRS). Nicotine (25 and 100 {mu}g/kg i.v.) dose-dependently reduced BRS{sub SNP} in contrast to no effect on BRS{sub PE}. BRS{sub SNP} was also attenuated after intracisternal (i.c.) administration of nicotine. Similar reductions in BRS{sub SNP} were observed in rats pretreated with atropine or propranolol. The combined treatment with nicotine and atropine produced additive inhibitory effects on BRS, an effect that was not demonstrated upon concurrent exposure to nicotine and propranolol. BRS{sub SNP} was reduced in preparations treated with i.c. 8-phenyltheophylline (8-PT, nonselective adenosine receptor antagonist), 8-(3-Chlorostyryl) caffeine (CSC, A{sub 2A} antagonist), or VUF5574 (A{sub 3} antagonist). In contrast, BRS{sub SNP} was preserved after blockade of A{sub 1} (DPCPX) or A{sub 2B} (alloxazine) receptors or inhibition of adenosine uptake by dipyridamole. CSC or 8-PT abrogated the BRS{sub SNP} depressant effect of nicotine whereas other adenosinergic antagonists were without effect. Together, nicotine preferentially impairs reflex tachycardia via disruption of adenosine A{sub 2A} receptor-mediated facilitation of reflex cardiac sympathoexcitation. Clinically, the attenuation by nicotine of compensatory sympathoexcitation may be detrimental in conditions such as hypothalamic defense response, posture changes, and ventricular rhythms. - Research Highlights: > The role of central adenosinergic sites in the nicotine-baroreflex interaction was investigated. > Inhibition of reflex sympathoinhibition mediates the BRS depressant action of nicotine. > Nicotine preferentially impairs reflex tachycardia via disruption of adenosine A{sub 2A} signaling. > The attenuation by nicotine of reflex sympathetic activity is clinically important.

• OSTI ID: 21587808
• Journal Information: Toxicology and Applied Pharmacology, Vol. 254, Issue 3; Other Information: DOI: 10.1016/j.taap.2011.04.014; PII: S0041-008X(11)00153-0; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADENOSINE
ATROPINE
BLOOD PRESSURE
CAFFEINE
CENTRAL NERVOUS SYSTEM
CONTROL
DIPYRIDAMOLE
DOSES
HAZARDS
HYPOTHESIS
INHIBITION
NICOTINE
RATS
RECEPTORS
SENSITIVITY
UPTAKE
ALKALOIDS
AMINES
ANALEPTICS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZINES
AZOLES
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM AGENTS
DRUGS
HETEROCYCLIC COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PARASYMPATHOLYTICS
PARASYMPATHOMIMETICS
PIPERIDINES
PROTEINS
PURINES
PYRIDINES
PYRROLES
PYRROLIDINES
RIBOSIDES
RODENTS
VASODILATORS
VERTEBRATES
XANTHINES