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(-5) M) were investigated in guinea pig isolated tracheal smooth muscle. Strips of guinea pig trachea, in some of which the epithelium had been removed mechanically, were suspended in organ chambers and isometric tension was recorded. ET-3 contracted 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 significantly 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 of VIP on ET-3-induced contraction of guinea pig isolated tracheal smooth muscle. On the other hand, the presence of tracheal epithelium was required for VIP (10(-8)) relaxation in Hist (10(-5)) contracted trachea. Apart from this finding, other Hist and all Ach-induced contractions (10(-5)) of the trachea were not significantly affected by ET-3 (10(-8)) or VIP treatments with or without epithelium. These findings indicate that VIP may play a role in inhibiting the contractile actions of ET-3 in guinea pig trachea and that an intact epithelium is not required for the relaxation but it is required for the VIP relaxation of Hist-induced contraction.