Non-genomic effect of testosterone on airway smooth muscle.
OBJECTIVE
Recent studies on blood vessels have provided evidence that testosterone may exert direct effects on smooth muscle. However, an acute effect on airway reactivity has not been shown yet. The aim of this study was to assess the direct effect of testosterone on the responsiveness of male adult rabbit airway smooth muscle (ASM), precontracted with 10 microM acetylcholine, 10microM carbachol or 80 mM KCl.


METHODS
Contractility studies of rabbit tracheal smooth muscle were performed.


RESULTS
Testosterone at concentrations of or above 1 nM had a significant relaxant effect on ASM precontracted with acetylcholine or carbachol, but did not affect ASM precontracted with KCl. The mechanical removal of airway epithelium as well as the inhibition of NO synthetase (by 100microM L-NAME) reduced the relaxation caused by testosterone. The effect of testosterone was not altered by impairing prostanoid synthesis (by 10microM indomethacin). The nitric oxide donor, sodium nitroprusside, had the same relaxant effect on ASM precontracted with either carbachol or KCl. Inhibitors of androgen receptors (10microM flutamide) or DNA transcription (100microM actinomycin D) did not alter the effect of testosterone. Prolonged incubation of ASM with 100 nM or 100 microM testosterone for 24 or 48 h did not alter their responsiveness to acetylcholine. BSA-testosterone (1pM to 100nM) relaxed significantly ASM precontracted with carbachol. The mechanical removal of airway epithelium abolished the relaxant effect of BSA-testosterone.


CONCLUSIONS
Testosterone relaxes precontracted ASM via an epithelium and NO-mediated way. This effect is mediated via a non-genomic pathway.
Kouloumenta
V
V
Department of Physiology, Medical School, University of Thessaly, Larissa, Greece. vakoul@med.uth.gr
Hatziefthimiou
A
A
Paraskeva
E
E
Gourgoulianis
K
K
Molyvdas
P A
PA
D000109:Acetylcholine / Q000494:pharmacology; D059002:Androgen Receptor Antagonists; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D009924:Organ Culture Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology; D011817:Rabbits; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D059002:Androgen Receptor Antagonists; D018721:Muscarinic Agonists; D011453:Prostaglandins; D014665:Vasodilator Agents; D009569:Nitric Oxide; D013739:Testosterone; D011189:Potassium Chloride; D002217:Carbachol; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine