The effect of the vasoactive intestinal polypeptide agonist Ro 25-1553 on induced tone in isolated human airways and pulmonary artery

Ro 25-1553 is a metabolically stable analogue of endogenous vasoactive inte stinal polypeptide (VIP). This compound is a potent bronchodilator in vitro as well as in vivo. Moreover, Ro 25-1553 has been shown to be highly selec tive of the VPAC(2) receptor. We assessed the effect of Ro 25-1553 on isola ted human bronchi and pulmonary arteries in vitro. Macroscopically normal h uman airways and pulmonary arteries were obtained from patients undergoing surgery for lung cancer. The relaxing capability of Ro 25-1553 on bronchial and pulmonary artery tone was measured using standard techniques. Bronchia l rings were pre-contracted with 0.1 mM histamine, and tone in pulmonary ar tery rings was induced with 10 muM PGF2 alpha. Increasing concentrations of Ro 25-1553 within a range of 1 pM to 10 muM were added and isometric tensi on changes were recorded. Ro 25-1553 caused a concentration-dependent relax ation of airway and pulmonary artery preparations, with an EC50 of approxim ately 10 nM and a maximal relaxation of 70%-75% of the induced tone. The pr esence of VPAC(2) receptors in the two tissues, though low in density, was confirmed by in situ hybridization, immunocytochemistry and ligand binding. These findings indicate that the VIP analogue Ro 25-1553 may be useful in the treatment of asthma and/or chronic obstructive pulmonary diseases.