Hyperosmolarity-induced relaxation and prostaglandin release in guinea pig trachea in vitro.
In this study, a tracheal perfusion apparatus was used to investigate the nature of the relaxing factor released by hyperosmolarity on the epithelial side of guinea pig trachea. NaCl induced concentration-dependent relaxation. This relaxation was not affected when the trachea was preincubated with a vasoactive intestinal peptide (VIP) receptor antagonist or with the nitric oxide synthesis inhibitor N(G)-monomethyl-L-arginine (L-NMMA). When the prostaglandin synthesis was prevented by preincubation with the phospholipase A(2)-inhibitor quinacrine, or the cyclooxygenase inhibitor indomethacin, the maximal relaxation induced by NaCl was suppressed by 50% (P<0.05). Moreover, the prostaglandin E(2) concentration was four times higher (P<0.05) in the organ bath during the relaxations, whereas the nitric oxide concentration remained unchanged. In conclusion, increased osmolarity on the airway surface leads to the release of prostaglandins, which are involved in part in the hyperosmolarity-induced relaxation of airway smooth muscle. This might be relevant for asthmatic patients since prostaglandin may modulate the bronchoconstrictive response to hyperosmolar stimuli and exercise.
Hjoberg
J
J
Department of Medical Sciences, Clinical Physiology, University Hospital, S-751 85, Uppsala, Sweden. josephine.hjoberg@medsci.uu.se
Folkerts
G
G
van Gessel
S B
SB
Högman
M
M
Hedenstierna
G
G
Nijkamp
F P
FP
D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009994:Osmolar Concentration; D011453:Prostaglandins / Q000378:metabolism*; D011796:Quinacrine / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011453:Prostaglandins; D019323:omega-N-Methylarginine; D012965:Sodium Chloride; D019001:Nitric Oxide Synthase; D011796:Quinacrine; D015232:Dinoprostone; D007213:Indomethacin