Central adenosine signaling plays a key role in centrally mediated hypotension in conscious aortic barodenervated rats.

Abstract

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.

• Authors: Noha Nassar, Abdel A Abdel-Rahman
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 318 Issue 1 Pg. 255-61 (Jul 2006) ISSN: 0022-3565 [Print] United States
• PMID: 16595736 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Adenosine A2 Receptor Agonists
• Receptor, Adenosine A2A
• Clonidine

Topics

• Adenosine A2 Receptor Agonists
• Animals
• Aorta (drug effects, physiology)
• Autonomic Denervation (methods)
• Blood Pressure (drug effects, physiology)
• Clonidine (pharmacology)
• Consciousness (drug effects, physiology)
• Hypotension (chemically induced, physiopathology)
• Male
• Pressoreceptors (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Adenosine A2A (physiology)
• Signal Transduction (drug effects, physiology)