RELAXING EFFECTS OF VASOACTIVE-INTESTINAL-PEPTIDE (VIP) ON THE CONTRACTILE ACTIONS OF ENDOTHELIN-3, HISTAMINE, AND ACETYLCHOLINE IN ISOLATED GUINEA-PIG TRACHEAL SMOOTH-MUSCLE WITH OR WITHOUT EPITHELIUM

The role of VIP on the contractile effects of endothelin-3 (ET-3) (10( -8) M) or a combination of ET-3 plus histamine (Hist) (10(-5) M) or ET -3 plus acetylcholine (Ach) (10(-8) M) were investigated in guinea pig isolated tracheal smooth muscle. Strips of guinea pig trachea, in som e of which the epithelium had been removed mechanically, were suspende d in organ chambers and isometric tension was recorded. ET-3 contracte d the tracheal smooth muscle in a dose-dependent manner ranging from 2 x 10(-12) to 2 X 10(-8) M. The removal of the epithelium significantl y potentiated the ET-3-induced contractions. VIP significantly relaxed ET-3 contractile responses about 46 +/- 12% for the intact trachea (p < 0.05) and 39 +/- 6% for the rubbed trachea (p < 0.05). The removal of the epithelium did not significantly change the relaxation effect o f VIP on ET-3-induced contraction of guinea pig isolated tracheal smoo th muscle. On the other hand, the presence of tracheal epithelium was required for VIP (10(-8)) relaxation in Hist (10(-5)) contracted trach ea. Apart from this finding, other Hist and all Ach-induced contractio ns (10(-5)) of the trachea were not significantly affected by ET-3 (10 (-8)) or VIP treatments with or without epithelium. These findings ind icate that VIP may play a role in inhibiting the contractile actions o f ET-3 in guinea pig trachea and that an intact epithelium is not requ ired for the relaxation but it is required for the VIP relaxation of H ist-induced contraction.