EFFECTS OF ROLIPRAM AND SIGUAZODAN ON THE HUMAN ISOLATED BRONCHUS ANDTHEIR INTERACTION WITH ISOPRENALINE AND SODIUM-NITROPRUSSIDE

1 The effects of the selective inhibitors of cyclic AMP phosphodiester ase type IV (rolipram) and type III (siguazodan) and their interaction s with isoprenaline and sodium nitroprusside have been studied in the human isolated bronchus.2 On bronchi under resting tone rolipram was, in terms of potency (pD2 = 7.77 +/- 0.14, n = 8), very similar to isop renaline (pD2 = 7.31 +/- 0.12, n = 12) and salbutamol (pD2 = 7.12 +/- 0.17, n = 10) and approximately 10 fold more potent than siguazodan (p D2 = 6.80 +/- 0.12, n = 6). In terms of efficacy (E(max) expressed as percentage of maximal effect induced by theophylline 3 mm), both rolip ram and siguazodan were less efficient (E(max) = 74 +/- 6.7%, n = 8 an d 66 +/- 7.5%, n = 6, respectively) than isoprenaline (E(max) = 98 +/- 0.4%, n = 12) and salbutamol (E(max) = 83 +/- 2.4%, n = 10). 3 During precontraction induced by methacholine (3 x 10(-7) M) or acetylcholin e (10(-3) M), concentration-response curves to rolipram and siguazodan were shifted to the right and maximal effects reduced. Rolipram was m ore potent than siguazodan and, in terms of efficacy, it was less acti ve. 4 Rolipram 10(-8) and 10(-7) M but not siguazodan potentiated the effects of isoprenaline as shown by the shift to the left of the conce ntration-response curve to isoprenaline. Sodium nitroprusside-induced relaxation was not modified by either drug. 5 These results show that rolipram is a potent relaxant of the human isolated bronchus, potentia ting the effects of beta-adrenoceptor stimulation and suggest that, as previously demonstrated in other species (guinea-pig, cow) (Tomkinson et al., 1993), there may be a connection between the beta2-adrenocept or subtype, which predominate in human airway smooth muscle, and the c yclic AMP phosphodiesterase type IV.