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Adenosine A2A receptor plays a pivotal role in mediating clonidine hypotension in aortically barodenervated rats
Author(s) -
Nassar Noha Nagah,
AbdelRahman Abdel A
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb105-d
Subject(s) - clonidine , adenosine , agonist , imidazoline receptor , medicine , adenosine a2a receptor , adenosine receptor , endocrinology , pharmacology , chemistry , anesthesia , receptor
In a previous study, we have shown an important role of central adenosine in the hypotension caused by clonidine, a mixed α 2 /I 1 centrally acting antihypertensive agent. Intracisternal (i.c.) 8‐sulfophenyl theophylline (8‐SPT) abolished, while dipyridamole enhanced, clonidine‐evoked hypotension in conscious aortic barodenervated (ABD) rats. Since clonidine is a mixed α 2 /I 1 , we investigated whether the I 1 ‐ or the α 2 ‐mediated hypotension is dependent on central adenosine signaling. To this end, conscious ABD rats were instrumented 5 days earlier for femoral blood pressure recording and i.c administration of selective I 1 ( rilmenidine 25 μg/kg;n=6–7) or α 2 ( α‐methlnorepinephrine, αMNE, (4μg/kg; n= 6–7) agonist 30 min after central (i.c) adenosine receptor blockade (8‐SPT; 10 μg/kg) or aCSF . The hypotensive response elicited by rilmenidine (24 ± 5 mmHg) and α‐MNE (16 ± 3 mmHg) in aCSF pretreated animals was virtually abolished in 8‐SPT pretreated rats. We concluded that I 1 /α 2 ‐mediated hypotension is dependent on central adenosine signaling. We hypothesized that the A 2A is responsible for mediating clonidine‐evoked hypotension. In the same animal model, the hypotensive and bradycardic responses elicited by i.c clonidine (0.6 μg) were investigated 30 min after central (i.c) adenosine receptor A 2A blockade (SCH5826 0.5mg /kg, i.c; n=5) or aCSF . The hypotensive response to clonidine was abolished by SCH5826 compared to the respective control. In conclusion, adenosine is a key mediator of clonidine‐evoked hypotension specifically through the A 2A receptors. Mechanistic studies are underway to determine the cellular pathways mediating the receptors cross talk.