Hyperosmolarity decreases the relaxing potency of sodium nitroprusside on guinea-pig trachea by the release of superoxide anions.
Increased osmolarity of the airway surface has been shown to abolish the airway relaxant effects of inhaled nitric oxide in rabbits in vivo and in guinea-pig trachea in vitro.


OBJECTIVE
In this study, we used a guinea-pig tracheal perfusion method to investigate whether superoxide anions, which rapidly react with nitric oxide, could be responsible for the reduced effect of nitric oxide in hyperosmolar airways.


METHODS
Guinea-pig tracheas were constricted with carbachol (CCh) and then subjected to the nitric oxide donor sodium nitroprusside (SNP) under isoosmolar or hyperosmolar conditions. Hyperosmolarity was created by increasing the NaCl concentration of the buffer on the epithelial side of the airway.


RESULTS
The relaxation produced by SNP was significantly less following hyperosmolar challenge, with a relaxation by 31 +/- 7% in hyperosmolar conditions as compared to 53 +/- 6% under normal isoosmolar conditions (P<0.05). The experiment was then performed in the presence of superoxide dismutase (SOD) that reduces levels of superoxide anions. SOD restored the relaxing potency of SNP in hyperosmolar conditions back to normal, to 46 +/- 5%.


CONCLUSIONS
This study shows that superoxide anions are responsible for the reduced relaxing potency of the nitric oxide donor SNP following an intraluminal hyperosmolar challenge in guinea-pig trachea in vitro. The finding may form the basis for new treatment of patients not responding to treatment with inhaled nitric oxide.
Hjoberg
J
J
Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden.
Högman
M
M
Hedenstierna
G
G
D000818:Animals; D006168:Guinea Pigs; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D009994:Osmolar Concentration; D010477:Perfusion / Q000379:methods; D013482:Superoxide Dismutase / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D020030:Nitric Oxide Donors; D013481:Superoxides; D009599:Nitroprusside; D009569:Nitric Oxide; D013482:Superoxide Dismutase