Nitric oxide and prostanoid-dependent relaxation induced by angiotensin IIin the isolated precontracted mouse tracheal muscle and the role of potassium channels
Ey. Sipahi et al., Nitric oxide and prostanoid-dependent relaxation induced by angiotensin IIin the isolated precontracted mouse tracheal muscle and the role of potassium channels, PHARMAC RES, 42(1), 2000, pp. 69-74
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.