Resting tension affects eNOS activity in a calcium-dependent way in airways.
The alteration of resting tension (RT) from 0.5 g to 2.5 g increased significantly airway smooth muscle contractions induced by acetylcholine (ACh) in rabbit trachea. The decrease in extracellular calcium concentration [Ca2+]o from 2 mM to 0.2 mM reduced ACh-induced contractions only at 2.5 g RT with no effect at 0.5 g RT. The nonselective inhibitor of nitric oxide synthase (NOS), N(G)-nitro-L-arginine methyl ester (L-NAME) increased ACh-induced contractions at 2.5 g RT. The inhibitor of inducible NOS, S-methylsothiourea or neuronal NOS, 7-nitroindazole had no effect. At 2.5 g RT, the reduction of [Ca2+]o from 2 mM to 0.2 mM abolished the effect of L-NAME on ACh-induced contractions. The NO precursor L-arginine or the tyrosine kinase inhibitors erbstatin A and genistein had no effect on ACh-induced contractions obtained at 2.5 g RT. Our results suggest that in airways, RT affects ACh-induced contractions by modulating the activity of epithelial NOS in a calcium-dependent, tyrosine-phosphorylation-independent way.
Kitsiopoulou
Eudoxia
E
Department of Physiology, Medical School, University of Thessaly, Papakiriazi 22, 41222 Larissa, Greece.
Hatziefthimiou
Apostolia A
AA
Gourgoulianis
Konstantinos I
KI
Molyvdas
Paschalis-Adam
PA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D019833:Genistein / Q000494:pharmacology; D006873:Hydroquinones / Q000494:pharmacology; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011817:Rabbits; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D006873:Hydroquinones; D007191:Indazoles; D001120:Arginine; D019833:Genistein; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine; D002118:Calcium; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester; C048212:erbstatin