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CARDIOVASCULAR

Central Adenosine Signaling Plays a Key Role in Centrally Mediated Hypotension in Conscious Aortic Barodenervated Rats

Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina

We tested the hypothesis that clonidine-evoked hypotension is dependent on central adenosinergic pathways. Five groups of male, conscious, aortic baroreceptor-denervated (ABD) rats received clonidine (10 µg/kg i.v.) 30 min after i.v. 1) saline, 2) theophylline (10 mg/kg), or 3) 8-(p-sulfophenyl)theophylline (8-SPT) (2.5 mg/kg) or 1 h after i.p. 4) dipyridamole (5 mg/kg) or 5) an equal volume of sesame oil. Blockade of central (theophylline) but not peripheral (8-SPT) adenosine receptors abolished clonidine hypotension. In contrast, dipyridamole substantially enhanced the bradycardic response to clonidine. In additional groups, intracisternal (i.c.) dipyridamole (150 µg) and 8-SPT (10 µg) enhanced and abolished, respectively, clonidine (0.6 µg i.c.)-evoked hypotension. Because clonidine is a mixed I₁/₂ agonist, we also investigated whether adenosine signaling is linked to the I₁ or the _2A receptor by administering the selective I₁ (rilmenidine, 25 µg) or _2A [-methylnorepinephrine (-MNE), 4 µg] agonist 30 min after central adenosine receptor blockade (8-SPT; 10 µg i.c.) or artificial cerebrospinal fluid. The hypotensive response elicited by rilmenidine or -MNE was abolished in 8-SPT-pretreated rats. To delineate the role of the adenosine A_2A receptor in clonidine-evoked hypotension, i.c. clonidine (0.6 µg) was administered 30 min after central adenosine receptor A_2A blockade [5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-]-1,2,4-triazolo[1,5-c]-pyrimidine (SCH58261); 150 µg i.c.]. The latter virtually abolished the hypotensive and bradycardic responses elicited by clonidine. In conclusion, central adenosine A_2A signaling plays a key role in clonidine-evoked hypotension in conscious aortic barodenervated rats.

Address correspondence to: Dr. Abdel A. Abdel-Rahman, Department of Pharmacology and Toxicology, School of Medicine, East Carolina University, Greenville, NC 27834. E-mail: abdelrahmana{at}ecu.edu

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