EFFECTS OF ADENOSINE-ANALOGS ON TENSION AND CYTOSOLIC CA2-ARTERY( IN PORCINE CORONARY)

This study evaluates the relaxing effects of adenosine analogues in re lation to intracellular free Ca2+ concentration ([Ca2+](i)) in porcine coronary artery. Changes in muscle tension and [Ca2+](i) were measure d simultaneously using the fluorescent Ca2+ indicator, fura 2-acetoxym ethyl ester. The ratio of fluorescence due to excitation at 340 nm to that at 380 nm reflects [Ca2+](i). Increased tension of the porcine co ronary artery contracted with prostaglandin F-2 alpha (PGF(2 alpha), 2 0 mu M) was accompanied by increased [Ca2+]i. The adenosine analogues, N-6-cyclopentyladenosine (CPA), 2-chloroadenosine (CAD), and yethyl)p henylamino]-5'-N-ethylcarboxamidoadenosine (CGS-22988) produced a conc entration-dependent (10(-8)-10(-4) M) reduction of [Ca2+](i) and tensi on with a maximum relaxation of similar to 96% and a [Ca2+](i) decreas e of 88% at a concentration of 10(-4) M. The order of potency for rela xation was CAD > CGS-22988 = CPA. Adenosine receptor antagonists (8-ph enyltheophylline, 10(-6) M; CGS-15943, 10(-5) M) shifted the agonist-m ediated relaxation and [Ca2+]i curve to the right in a parallel fashio n. In Ca2+-free buffer, PGF(2 alpha), (20 mu M)-induced contraction wa s significantly reduced (75%). PGF(2 alpha), also caused a transient i ncrease in [Ca2+](i) that later was reduced below the resting level. T he order of potency for relaxation for adenosine analogues in Ca2+-fre e buffer was found to be CAD = CGS-22988 > CPA. All curves were shifte d to the right in the presence of receptor antagonists. These results indicate that adenosine receptor-mediated changes in [Ca2+](i) and rel axation in porcine coronary smooth muscle are at least partly independ ent of extracellular Ca2+.