Effects of inhibitors of small- and intermediate-conductance calcium-activated potassium channels, inwardly-rectifying potassium channels and Na+/K+ ATPase on EDHF relaxations in the rat hepatic artery

1 In the rat hepatic artery, the SKCa inhibitors UCL 1684 (300 nM) complete ly blocked, and scyllatoxin (1 mu M) and d-tubocurarine (100 mu M) partiall y inhibited EDHF relaxations when each of them was combined with charybdoto xin (300 nM). 2 The IKCa inhibitors clotrimazole (3 mu M) and 2-chlorophenyl-bisphenyl-me thanol (3 mu M) strongly depressed EDHF relaxations when each of them was c ombined with apamin (300 nM). The cytochrome P450 mono-oxygenase inhibitor ketoconazole (10 mu M) had no effect in the presence of apamin. 3 Ciclazindol (10 mu M), which abolishes EDHF relaxations in the presence o f apamin, almost completely prevented the calcium ionophore (A23187) stimul ated Rb-86(+) influx tin the Gardos channel (IKCa) in human erythrocytes. 4 The Na+/K+ ATPase inhibitor ouabain (500 mu M) and the K-IR blocker Ba2(30 mu M) neither alone nor in combination inhibited EDHF relaxations. Ba2 was also without effect in the presence of either apamin or charybdotoxin. 5 In contrast to EDHF, an increase in extracellular [K+] from 4.6 mM to 9.6 , 14.6 and 19.6 mM inconsistently relaxed arteries. In K+-free physiologica l salt solution, re-admission of K+ always caused complete and sustained re laxations which were abolished by ouabain but unaffected by Ba26 The present study provides pharmacological evidence for the involvement o f SKCa and IKCa in the action of EDHF in the rat hepatic artery. Our result s are not consistent with the idea that EDHF is K+ activating Na+/K+ ATPase and K-IR in this blood vessel.