Nitric oxide and prostanoid-dependent relaxation induced by angiotensin II in the isolated precontracted mouse tracheal muscle and the role of potassium channels.
In this study we examined the mechanism of the concentration-dependent relaxant effect of angiotensin II (A II) on mouse isolated tracheal rings precontracted by carbachol. The contractile effect of carbachol is increased while the relaxant effect of A II decreased by pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME). This finding suggests that the L-arginine nitric 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 the isolated tracheal rings precontracted by K(+)(>60 m m). K(+)-channel blockers partially inhibited the relaxant effect of A II in carbachol-precontracted mouse tracheal rings. A non-selective blocker of K(+)channels, tetraethylammonium, completely abolished the relaxation induced by A II. Among the other channel blockers, the inhibitory effect of apamine and glibenclamide was 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 induced by A II in the isolated mouse tracheal rings precontracted by carbachol, were firstly l -arginine NO and cyclo-oxygenase products of arachidonic acid, secondly K(+)channels.
Sipahi
E Y
EY
Department of Pharmacology, Faculty of Medicine, Gazi University, Ankara, Turkey.
Türker
R K
RK
Ercan
Z S
ZS
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D015221:Potassium Channels; D011453:Prostaglandins; D000804:Angiotensin II; D009569:Nitric Oxide; D002217:Carbachol; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester