Nitric oxide and prostanoid-dependent relaxation induced by angiotensin IIin the isolated precontracted mouse tracheal muscle and the role of potassium channels

In this study we examined the mechanism of the concentration-dependent rela xant effect of angiotensin II (A II) on mouse isolated tracheal rings preco ntracted by carbachol. The contractile effect of carbachol is increased whi le the relaxant effect of A II decreased by pretreatment with N-G-nitro-L-a rginine methyl ester (L-NAME). This finding suggests that the L-arginine ni tric oxide (NO) pathway is activated by the peptide. The relaxing effect of A II was also mediated through the release of cyclo-oxygenase products of arachidonic acid, as evidenced by the inhibition of the response by lysine acetylsalicylic acid (ASA) pretreatment. A II also caused a relaxation in t he isolated tracheal rings precontracted by K+ (> 60 mM). K+-channel blocke rs partially inhibited the relaxant effect of A II in carbachol-precontract ed mouse tracheal rings. A non-selective blocker of K+ channels, tetraethyl ammonium, completely abolished the relaxation induced by A II. Among the ot her channel blockers, the inhibitory effect of apamine and glibenclamide wa s higher than that of iberiotoxin, indicating the involvement of K-ATP and small conductance K-Ca channels in the relaxing response to the octapeptide . These results suggest that the mechanisms, involved in the relaxation ind uced by A II in the isolated mouse tracheal rings precontracted by carbacho l, were firstly L-arginine NO and cyclo-oxygenase products of arachidonic a cid, secondly K+ channels. (C) 2000 Academic Press.