Metabolism of cAMP to adenosine: role in vasodilation of rat pial artery in response to hypotension.

Abstract

The purpose of this experiment was to examine whether the cAMP-adenosine pathway is implicated in the autoregulatory vasodilation in response to hypotension. Suffusion with cAMP (1-100 micromol/l) or adenosine (0.01-10 micromol/l) caused a sustained vasodilation of the resting pial arteries in a concentration-dependent manner. In contrast, N6,2'-O-dibutyryl-cAMP and 8-bromo-cAMP exerted a weak dilation at high concentration (100 micromol/l). The vasodilation to cAMP (1-100 micromol/l), adenosine (0.01-10 micromol/l), and hypotension was significantly reduced by pretreatment with 3,7-dimethyl-1-propargylxanthine (1 micromol/l), an A2 receptor antagonist, as well as 3-isobutyl-1-methylxanthine (3 micromol/l), an inhibitor of endo- and ectophosphodiesterase, 1, 3-dipropyl-8-p-sulfophenylxanthine (100 micromol/l), an inhibitor of ecto-5'-phosphodiesterase, or alpha,beta-methylene-adenosine 5'-diphosphate (100 micromol/l), an inhibitor of ecto-5'-nucleotidase. However, 8-cyclopentyltheophylline (1 micromol/l), an A1 antagonist, did not elicit a similar response. The increased release of adenosine when the cortical surface was suffused with cAMP (100 micromol/l) was significantly reduced by 3-isobutyl-1-methylxanthine, 1,3-dipropyl-8-p-sulfophenylxanthine, and alpha,beta-methylene-adenosine 5'-diphosphate (each 100 micromol/l). These results indicate that the cAMP-adenosine pathway as a viable metabolic mechanism is implicated in the production of adenosine in the rat pial artery and contributes to the regulation of vasodilation in response to hypotension.

• Authors: K W Hong, H K Shin, H H Kim, J M Choi, B Y Rhim, W S Lee
• Journal: The American journal of physiology (Am J Physiol) Vol. 276 Issue 2 Pg. H376-82 (02 1999) ISSN: 0002-9513 [Print] United States
• PMID: 9950836 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Purinergic P1 Receptor Antagonists
• Cyclic AMP
• Adenosine

Topics

• Adenosine (metabolism)
• Animals
• Cerebral Arteries (physiopathology)
• Cyclic AMP (analogs & derivatives, metabolism, physiology)
• Enzyme Inhibitors (pharmacology)
• Homeostasis (physiology)
• Hypotension (physiopathology)
• Male
• Pia Mater (blood supply)
• Purinergic P1 Receptor Antagonists
• Rats
• Rats, Sprague-Dawley
• Vasodilation (drug effects, physiology)