Mechanism of adenosine-induced vasodilation in rat diaphragm microcirculation

The mechanism of adenosine-induced vasodilation in rat diaphragm microcircu lation was investigated using laser Doppler flowmetry. Adenosine (10(-5), 3 .2 x 10(-5), and 10(-4) M), the nonselective adenosine agonist 5'-N-ethylca rboxamido-adenosine (NECA) (10(-8)-10(-7) M), the specific A(2A) agonist 2- p-(2-carboxyethyl)phenylamino-5'-N-ethyl carboxamidoadenosine (CGS-21680) ( 10(-8)-10(-7) M), and the adenosine agonist with higher A(1)-receptor affin ity, R-N-6-phenylisopropyladenosine (R-PIA) (10(-7), 3.2 x 10(-7), and 10(- 6) M) elicited a similar degree of incremental increase of microcirculatory flow in a dose-dependent manner. The ATP-dependent potassium (K-ATP) chann el blocker glibenclamide (3.2 x 10(-6) M) significantly attenuated the vaso dilation effects of these agonists. Adenosine-induced vasodilation could be significantly attenuated by the nonselective adenosine antagonist 8-(p-sul fophenyl)-theophylline (3 x 10(-5) M) or the selective A(2A) antagonist 4-( 2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5] triazin-5-ylamino]ethyl ) phenol (ZM-241385, 10(-6) M), but not by the selective A(1) antagonist 8- cyclopentyl-1,3-dipropylxanthine (5 x 10(-8) M). Adenylate cyclase inhibito r N-(cis-2-phenyl-cyclopentyl) azacyclotridecan-2-imine-hydrochloride (MDL- 12330A, 10(-5) M) effectively suppressed the vasodilator response of adenos ine and forskolin. These results suggest that adenosine-induced vasodilatio n in rat diaphragm microcirculation is mediated through the stimulation of A(2A) receptors, which are coupled to adenylate cyclase activation and open ing of the KATP channel.