Vasodilation produced by forskolin compared with that produced by adenosine in rabbit coronary artery

We compared the relaxing action of forskolin with that of adenosine in rabbit coronary artery and analyzed the pharmacological properties of this effect of forskolin. In preparations of this artery precontracted by 10-16 mM KCl, the addition of forskolin (10(-9)-10(-5) M) and adenosine (10(-9)-10(-4) M) to the organ bath produced dose-dependent relaxations. The mean EC50 for the relaxing action of forskolin was 4.5 X 10(-8) M and that of adenosine was 3.6 X 10(-7) M, forskolin being 10 times more potent than adenosine. Relaxation produced by forskolin was not affected by treatment with propranolol (10(-5) M), atropine (10(-6) M), or 8-phenyltheophylline (10(-6) M), but was competitively inhibited by ouabain (10(-6) M). The relaxation produced by adenosine was inhibited by 8-phenyltheophylline (10(-6) M) competitively and by ouabain (10(-6) M) noncompetitively. In preparations precontracted by a higher concentration of KCl, 40 mM, forskolin produced full relaxation with a shift of the dose-response curve to the right; adenosine did not produce full relaxation. Both forskolin and adenosine attenuated the maximum contraction produced by Ca2+. These findings indicate that the vasorelaxing effect of forskolin was not due to activation of beta-adrenoceptors, muscarinic receptors, or adenosine receptors, whereas that of adenosine was due to activation of adenosine receptors. Increased availability of intracellular Ca2+ competitively inhibited the relaxation induced by forskolin and noncompetitively inhibited the relaxation induced by adenosine. Both forskolin and adenosine noncompetitively inhibited contraction induced by Ca2+.