Central adenosine signaling plays a key role in centrally mediated hypotension in conscious aortic barodenervated rats.
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 microg/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 microg) and 8-SPT (10 microg) enhanced and abolished, respectively, clonidine (0.6 microg i.c.)-evoked hypotension. Because clonidine is a mixed I1/alpha2 agonist, we also investigated whether adenosine signaling is linked to the I1 or the alpha2A receptor by administering the selective I1 (rilmenidine, 25 microg) or alpha2A [alpha-methylnorepinephrine (alpha-MNE), 4 microg] agonist 30 min after central adenosine receptor blockade (8-SPT; 10 microg i.c.) or artificial cerebrospinal fluid. The hypotensive response elicited by rilmenidine or alpha-MNE was abolished in 8-SPT-pretreated rats. To delineate the role of the adenosine A2A receptor in clonidine-evoked hypotension, i.c. clonidine (0.6 microg) was administered 30 min after central adenosine receptor A2A blockade [5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-epsilon]-1,2,4-triazolo[1,5-c]-pyrimidine (SCH58261); 150 microg i.c.]. The latter virtually abolished the hypotensive and bradycardic responses elicited by clonidine. In conclusion, central adenosine A2A signaling plays a key role in clonidine-evoked hypotension in conscious aortic barodenervated rats.
Nassar
Noha
N
Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Abdel-Rahman
Abdel A
AA
D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D017763:Autonomic Denervation / Q000379:methods; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D003243:Consciousness / Q000187:drug effects / Q000502:physiology*; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D058908:Adenosine A2 Receptor Agonists; D043705:Receptor, Adenosine A2A; D003000:Clonidine