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

The purpose of this experiment was to examine whether the cAMP-adenosine pa thway is implicated in the autoregulatory vasodilation in response to hypot ension. Suffusion with cAMP (1-100 mu mol/l) or adenosine (0.01-10 mu mol/l ) caused a sustained vasodilation of the resting pial arteries in a concent ration-dependent manner. In contrast, N-6,2'-O-dibutyryl-cAMP and 8-bromo-c AMP exerted a weak dilation at high concentration (100 mu mol/l). The vasod ilation to cAMP (1-100 mu mol/l), adenosine (0.01-10 mu mol/l), and hypoten sion was significantly reduced by pretreatment with 3,7-dimethyl-1-propargy lxanthine (1 mu mol/l), an A(2) receptor antagonist, as well as S-isobutyl- l-methylxanthine (3 mu mol/l), an inhibitor of endo- and ectophosphodiester ase, 1,3-dipropyl-8-p-sulfophenylxanthine (100 mu mol/l), an inhibitor of e cto-5'-phosphodiesterase, or alpha,beta-methylene-adenosine 5'-diphosphate (100 mu mol/l), an inhibitor of ecto-5'-nucleotidase. However, 8-cyclopenty ltheophylline (1 mu mol/l), an A(1) antagonist, did not elicit a similar re sponse. The increased release of adenosine when the cortical surface was su ffused with cAMP (100 mu mol/l) was significantly reduced by 3-isobutyl-1-m ethylxanthine, 1,3-dipropyl-8-p-sulfophenylxanthine, and alpha,beta-methyle ne-adenosine 5'-diphosphate (each 100 mu mol/l). These results indicate tha t the cAMP-adenosine pathway as a viable metabolic mechanism is implicated in the production of adenosine in the rat pial artery and contributes to th e regulation of vasodilation in response to hypotension.