INHIBITION OF ADENOSINE-INDUCED CORONARY VASODILATION BY BLOCK OF LARGE-CONDUCTANCE CA2+-ACTIVATED K+ CHANNELS

The aim of the present study was to investigate the contribution of large-conductance calcium-activated potassium (large-conductance K-Ca) channels to adenosine (Ado)- and nitroprusside-mediated relaxation in small coronary arteries. Canine subepicardial arteries (170 +/- 23 mu m at 120 mmHg) were studied as in vitro pressurized vessels. Pressure-diameter experiments showed myogenic tone over a physiological range of pressures. Tone was increased with the thromboxane A(2) analogue 9,11-dideoxy-11 alpha,9 alpha-epoxy-methanoprostaglandin F-2 alpha (U-46619). Tetraethylammonium (TEA(+); 1 mM) significantly inhibited Ado-induced [and by implication, adenosine 3',5'-cyclic monophosphate (cAMP)-induced] relaxations at Ado concentrations ranging from 0.1 to 10 mu M with maximal inhibition (61 +/- 8%) at 1 mu M Ado. The large-conductance K-Ca-channel blocker iberiotoxin (IbTX; 0.01-0.1 mu M) inhibited Ado-mediated relaxation in a concentration-dependent manner. Inhibition by IbTX increased with increasing vessel pressure (i.e., 45 +/- 12% at 40 mmHg and 83 +/- 20% at 120 mmHg). TEA(+) had a minimal effect (8 +/- 3%) on relaxation induced by nitroprusside. Similar results were found with acetylcholine and bradykinin. These results suggest that (in dog coronary arteries with diameter < 200 mu m) large-conductance K-Ca-channel modulation may play a major role in cAMP-mediated relaxation but is not significant in guanosine 3',5'-cyclic monophosphate-mediated relaxation.