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 μm 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 A₂ analogue 9,11-dideoxy-11α,9α-epoxy- methanoprostaglandin F(2α) (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 μM with maximal inhibition (61 ± 8%) at 1 μM Ado. The large-conductance K(Ca)-channel blocker iberiotoxin (IbTX; 0.01-0.1 μM) 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 μm) 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.