Effect of potassium channel blockers on relaxations to a nitric oxide donor and to nonadrenergic nerve stimulation in guinea pig trachea.

Nonadrenergic, noncholinergic (NANC) relaxations were elicited by field stimulation (1-16 Hz, 1 msec, 12 V for 15 sec) of guinea pig trachea desensitized with capsaicin (3 microM); pretreated with atropine (1 microM), propranolol (1 microM), indomethacin (3 microM) and alpha-chymotrypsin (2 U/ml) and contracted with 3 microM histamine. The nitric oxide (NO) synthase inhibitor L-nitro-N-arginine (L-NNA) significantly inhibited these responses, which is indicative of NO involvement. The ability of the large conductance Ca(++)-activated K+ channel antagonists iberiotoxin (IbTx) and charybdotoxin (ChTx) and the small conductance Ca(++)-activated K+ channel antagonist apamin to modify relaxations to NANC nerve stimulation and to the NO donor 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1) was studied. Both IbTx (100 nM) and ChTx (100 nM) were found to inhibit the L-NNA-sensitive relaxations elicited by field stimulation and to inhibit the relaxations to SIN-1. In contrast, apamin did not inhibit the relaxations to either field stimulation or SIN-1. These results suggest that in the guinea pig trachea, responses to endogenous or exogenously added NO are at least in part mediated by the large conductance Ca(++)-activated K+ channel.