Mechanism of adenosine-induced vasodilation in rat diaphragm microcirculation

Abstract

The mechanism of adenosine-induced vasodilation in rat diaphragm microcirculation was investigated using laser Doppler flowmetry. Adenosine (10−5, 3.2 × 10−5, and 10−4 M), the nonselective adenosine agonist 5′- N-ethylcarboxamido-adenosine (NECA) (10−8-10−7 M), the specific A2Aagonist 2- p-(2-carboxyethyl)phenyl-amino-5′- N-ethyl carboxamidoadenosine (CGS-21680) (10−8-10−7M), and the adenosine agonist with higher A1-receptor affinity, R- N 6-phenylisopropyladenosine ( R-PIA) (10−7, 3.2 × 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 (KATP) channel blocker glibenclamide (3.2 × 10−6 M) significantly attenuated the vasodilation effects of these agonists. Adenosine-induced vasodilation could be significantly attenuated by the nonselective adenosine antagonist 8-( p-sulfophenyl)-theophylline (3 × 10−5M) or the selective A2A 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 A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (5 × 10−8 M). Adenylate cyclase inhibitor N-( cis-2-phenyl-cyclopentyl) azacyclotridecan-2-imine-hydrochloride (MDL-12330A, 10−5M) 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 A2A receptors, which are coupled to adenylate cyclase activation and opening of the KATP channel.