Chen, Chang-Wen, Han-Yu Chang, and Tzuen-Ren Hsiue. Mechanism of adenosine-induced vasodilation in rat diaphragm microcirculation. Am J Physiol Heart Circ Physiol 279: H2210-H2217, 2000.--The mechanism of adenosineinduced vasodilation in rat diaphragm microcirculation was investigated using laser Doppler flowmetry. Adenosine ([10.sup.-5], 3.2 x [10.sup.-5], and [10.sup.-4] M), the nonselective adenosine agonist 5'-N-ethylcarboxamido-adenosine (NECA) ([10.sup.-8] - [10.sup.-7] M), the specific [A.sub.2A] agonist 2-p-(2-carboxyethyl)phenyl-amino-5' -N-ethyl carboxamidoadenosine (CGS-21680) ([10.sup.-8] - [10.sup.-7] M), and the adenosine agonist with higher [A.sub.1]-receptor affinity, R-[N.sup.6]-phenylisopropyladenosine (R-PIA) ([10.sup.-7], 3.2 X [10.sup.-7], and [10.sup.-6] M) elicited a similar degree of incremental[ increase of microcirculatory flow in a dose-dependent manner. The ATP-dependent potassium ([K.sub.ATP) channel blocker glibenclamide (3.2 x [10.sup.-6] M) significantly attenuated the vasodilation effects of these agonists. Adenosine-induced vasodilation could be significantly attenuated by the nonselective adenosine antagonist 8-(p-sulfophenyl)-theophy]line (3 x [10.sup.-5] M) or the selective [A.sub.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.sub.1] antagonist 8-cyclopentyl-l,3-dipropylxanthine (5 x [10.sup.-8] M). Adenylate cyclase inhibitor N-(cis-2-phenyl-cyclopentyl) azacyclotridecan-2-imine-hydrochloride (MDL-12330A, [10.sup.-5]M) effectively suppressed the vasodilator response of adenosine and forskolin. These results suggest that adenosine-induced vasodilation in rat diaphragm microcirculation is mediated through the stimulation of [A.sub.2A] receptors, which are coupled to adenylate cyclase activation and opening of the [K.sub.ATP] channel. blood flow; glibenclamide; laser Doppler flowmetry; skeletal muscle