Endogenous nitric oxide modulation of potassium-induced changes in guinea-pig airway tone.
1. An experimental set up is used whereby the serosal (out)side or mucosal (in)side of the guinea-pig isolated tracheal tube can be stimulated selectively with drugs and reactivity measured. 2. Potassium induces a concentration-dependent (5-70 mM) monophasic contraction of tracheal tubes when added on the outside. In contrast, on the inside, potassium induces a concentration-dependent relaxation at low concentrations (5-40 mM) which was reversed into a contraction up to approximately basal tone at higher concentrations (50-70 mM). 3. Epithelium denudation reversed the potassium-induced relaxation into a contraction. Interestingly, in the 'half' epithelium-denuded trachea the contractions were significantly (P < 0.01) reduced by 46% compared to complete epithelium-denuded tissues. 4. Incubation with the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 120 microM) for 30 min on the inside of the tracheal tube completely prevented the relaxation. However, L-NAME did not reverse the potassium-induced relaxation into a contraction. This indicates that potassium does not penetrate through the epithelial layer. 5. It is concluded that depolarization of smooth muscle cells leads to a monophasic contraction and that depolarization of the epithelium leads to a relaxation of tracheal smooth muscle. The epithelial layer has an important barrier function and can release relaxing factors like NO.
Folkerts
G
G
Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
van der Linde
H
H
Verheyen
A K
AK
Nijkamp
F P
FP
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011188:Potassium / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester