Effects of adenosine analogues on tension and cytosolic Ca2+ in porcine coronary artery.

This study evaluates the relaxing effects of adenosine analogues in relation to intracellular free Ca2+ concentration ([Ca2+]i) in porcine coronary artery. Changes in muscle tension and [Ca2+]i were measured simultaneously using the fluorescent Ca2+ indicator, fura 2-acetoxymethyl ester. The ratio of fluorescence due to excitation at 340 nm to that at 380 nm reflects [Ca2+]i. Increased tension of the porcine coronary artery contracted with prostaglandin F2 alpha (PGF2 alpha, 20 microM) was accompanied by increased [Ca2+]i. The adenosine analogues, N6-cyclopentyladenosine (CPA), 2-chloroadenosine (CAD), and 2-[m-(carboxyethyl)-phenylamino]-5'-N-ethylcarboxamidoadenosine (CGS-22988) produced a concentration-dependent (10(-8)-10(-4) M) reduction of [Ca2+]i and tension with a maximum relaxation of approximately 96% and a [Ca2+]i decrease of 88% at a concentration of 10(-4) M. The order of potency for relaxation was CAD > CGS-22988 = CPA. Adenosine receptor antagonists (8-phenyltheophylline, 10(-6) M; CGS-15943, 10(-5) M) shifted the agonist-mediated relaxation and [Ca2+]i curve to the right in a parallel fashion. In Ca(2+)-free buffer, PGF2 alpha (20 microM)-induced contraction was significantly reduced (75%). PGF2 alpha also caused a transient increase in [Ca2+]i that later was reduced below the resting level. The order of potency for relaxation for adenosine analogues in Ca(2+)-free buffer was found to be CAD = CGS-22988 > CPA. All curves were shifted to the right in the presence of receptor antagonists. These results indicate that adenosine receptor-mediated changes in [Ca2+]i and relaxation in porcine coronary smooth muscle are at least partly independent of extracellular Ca2+.