POTENTIATION OF THE BRONCHOPROTECTIVE EFFECTS OF VASOACTIVE-INTESTINAL-PEPTIDE, ISOPRENALINE, AND THEOPHYLLINE AGAINST HISTAMINE CHALLENGE IN ANESTHETIZED GUINEA-PIGS BY ADRENOMEDULLIN

Background - Adrenomedullin is a hypotensive peptide recently discover ed in human phaeochromocytoma which has been found to inhibit bronchoc onstriction induced by histamine and acetylcholine. This study was des igned to determine the manner in which adrenomedullin and other bronch odilators interact in modulating airway function. Methods - A study wa s undertaken to determine whether adrenomedullin potentiated the bronc hoprotective effects of isoprenaline, vasoactive intestinal peptide (V IP), and theophylline against histamine-induced bronchoconstriction in anaesthetised guinea pigs in vivo. Results - Adrenomedullin in a conc entration of 10(-9) M significantly inhibited histamine-induced bronch oconstriction but in a concentration of 10(-10) M it did not exhibit t he bronchoprotective effect against histamine. VIP (10(-9) M) did not affect histamine-induced bronchoconstriction but it markedly inhibited the bronchoprotective effect against histamine in the presence of adr enomedullin (10(-10) M). VIP (10(-6) M) significantly inhibited histam ine-induced bronchoconstriction but this effect was short lived. Adren omedullin in a concentration of 10(-10) M potentiated bronchoprotectio n induced by VIP (10(-6) M) and prolonged it. Isoprenaline (10(-8) M) also significantly inhibited histamine-induced bronchoconstriction and this effect was enhanced of adrenomedullin Similarly, adrenomedullin (10(-10) M) significantly potentiated theophylline-induced bronchoprot ection, and a sub-bronchoprotective dose of theophylline (20 mg/kg i.p .) was effective in preventing histamine-induced bronchoconstriction i n the presence of adrenomedullin (10(-10) M). Conclusions - This study shows that adrenomedullin potentiates the bronchoprotective effects o f different classes of bronchodilators against histamine challenge in anaesthetised guinea pigs.