INVOLVEMENT OF A GLIBENCLAMIDE-SENSITIVE MECHANISM IN THE NITRERGIC NEUROTRANSMISSION OF THE PIG INTRAVESICAL URETER

1 The present study was designed to investigate whether potassium (K+) channels are involved in the relaxations to nitric oxide (NO) of pig intravesical ureteral preparations suspended in organ baths for isomet ric tension recordings. In ureteral strips treated with guanethidine ( 10(-5) M) and atropine (10(-7) M) to block adrenergic neurotransmissio n and muscarinic receptors, respectively, NO was either released from nitrergic nerves by electrical field stimulation (EFS, 0.5-10 Hz, 1 ms duration, 20 s trains), or exogenously-applied as an acidified soluti on of sodium nitrite (NaNO2, 10(-6)-10(-3) M). 2 Incubation with an in hibitor of guanylate cyclase activation by NO, methylene blue (10(-5) M) did not change the basal tension of intravesical ureteral strips bu t inhibited the relaxation induced by EFS or exogenous NO on ureteral preparations contracted with the thromboxane analogue U46619 (10(-7) M ). 3 Incubation with charybdotoxin (3 x 10(-8) M) and apamin (5 x 10(- 7) M), which are inhibitors of large and small conductance calcium (Ca 2+)-activated K+ channels, respectively, did not modify basal tension or the relaxations induced by EFS and exogenous NO. Treatment with cha rybdotoxin or apamin plus methylene blue (10(-5) M) significantly redu ced the relaxations to EFS and exogenous NO. However, in both cases th e reductions were similar to the inhibition evoked by methylene blue a lone. The combined addition of charybdotoxin plus apamin did not chang e the relaxations to EFS or exogenously added NO of the porcine intrav esical ureter. 4 Cromakalim (10(-8)-3 x 10(-6) M), an opener of ATP-se nsitive K+ channels, evoked a dose-dependent relaxation with a pot of 7.3+/-0.2 and maximum relaxant effect of a 71.8+/-4.2% of the contract ion induced by U46619 in the pig intravesical ureter. The blocker of A TP-sensitive K+ channels, glibenclamide (10(-6) M), inhibited markedly the relaxations to cromakalim. 5 Glibenclamide (10(-6) M) had no effe ct on the basal tone of ureteral preparations but significantly reduce d the relaxations induced by both EFS and exogenous NO. Combined treat ment with methylene blue (10(-5) M) and glibenclamide (10(-6) M) did n ot exert an effect greater than that of methylene blue alone on either EFS- or NO-evoked relaxations of the pig ureter. 6 The present result s suggest that NO acts as an inhibitory neurotransmitter in the pig in travesical ureter and relaxes smooth muscle through a guanylate cyclas e-dependent mechanism which seems to Favour the opening of glibenclami de-sensitive K+ channels.