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

Abstract

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 uptakemore » 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.« less

Authors:
; ; ;
Publication Date:
OSTI Identifier:
21587808
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 254; Journal 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)
Country of Publication:
United States
Language:
English
Subject:
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

Citation Formats

El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com, El-gowilly, Sahar M., Fouda, Mohamed A., and Saad, Evan I. Role of adenosine A{sub 2A} receptor signaling in the nicotine-evoked attenuation of reflex cardiac sympathetic control. United States: N. p., 2011. Web. doi:10.1016/j.taap.2011.04.014.
El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com, El-gowilly, Sahar M., Fouda, Mohamed A., & Saad, Evan I. Role of adenosine A{sub 2A} receptor signaling in the nicotine-evoked attenuation of reflex cardiac sympathetic control. United States. doi:10.1016/j.taap.2011.04.014.
El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com, El-gowilly, Sahar M., Fouda, Mohamed A., and Saad, Evan I. Mon . "Role of adenosine A{sub 2A} receptor signaling in the nicotine-evoked attenuation of reflex cardiac sympathetic control". United States. doi:10.1016/j.taap.2011.04.014.
@article{osti_21587808,
title = {Role of adenosine A{sub 2A} receptor signaling in the nicotine-evoked attenuation of reflex cardiac sympathetic control},
author = {El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com and El-gowilly, Sahar M. and Fouda, Mohamed A. and Saad, Evan I.},
abstractNote = {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.},
doi = {10.1016/j.taap.2011.04.014},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 254,
place = {United States},
year = {Mon Aug 01 00:00:00 EDT 2011},
month = {Mon Aug 01 00:00:00 EDT 2011}
}