Anti-edema action of formoterol in rat trachea does not depend on capsaicin-sensitive sensory nerves.
The beta 2-adrenergic agonist formoterol has been shown to inhibit plasma extravasation in the respiratory mucosa associated with neurogenic inflammation as well as that caused by histamine or bradykinin. It is unknown whether these effects of formoterol are mediated through an action of sensory nerves or through a direct effect on the leaky blood vessels. In the present study we sought to determine whether capsaicin-sensitive sensory nerves are essential for the anti-edema effect of formoterol in the rat trachea. Substance P (5 micrograms/kg), PAF (hexadecyl-PAF, 5 micrograms/kg), or bradykinin (10 mg/kg) was injected intravenously to increase vascular permeability. The amount of plasma extravasation was measured with two tracers, Evans blue dye and Monastral blue pigment. The effectiveness of formoterol's anti-edema action was assessed in two groups of rats. One was pretreated with capsaicin to eliminate tachykinin-containing sensory nerves and another, the control group, was not pretreated. We found that in control rats formoterol inhibited to a similar extent the extravasation of Evans blue and Monastral blue caused by all three mediators. The highest intravenous dose of formoterol (10 micrograms/kg) reduced substance P-induced extravasation of Monastral blue by 59%, reduced PAF-induced extravasation by 74%, and reduced bradykinin-induced extravasation by 58%. Pretreatment of rats with a dose of capsaicin that eliminated at least 94% of the substance P-immunoreactive nerve fibers did not significantly reduce the effectiveness of formoterol against any of the mediators.(ABSTRACT TRUNCATED AT 250 WORDS)
Sulakvelidze
I
I
Cardiovascular Research Institute, University of California, San Francisco 94143.
McDonald
D M
DM
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001920:Bradykinin; D002199:Capillary Permeability / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D007275:Injections, Intravenous; D008297:Male; D010972:Platelet Activating Factor / Q000031:analogs & derivatives; D011292:Premedication; D051381:Rats; D011916:Rats, Inbred F344; D013373:Substance P; D014132:Trachea / Q000294:innervation*; D014133:Tracheal Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D010972:Platelet Activating Factor; D013373:Substance P; C037145:1-hexadecyl-2-acetyl-glycero-3-phosphocholine; D002211:Capsaicin; D001920:Bradykinin; D000068759:Formoterol Fumarate