POTENTIATION OF NONADRENERGIC NONCHOLINERGIC RELAXATION OF HUMAN ISOLATED BRONCHUS BY SELECTIVE INHIBITORS OF PHOSPHODIESTERASE ISOZYMES

Human bronchial rings were contracted with histamine (3 mu M), and inh ibitory responses were obtained with electrical field stimulation (EFS ) in the presence of propranolol (1 mu M), atropine (1 mu M), and indo methacin (3 mu M). These nonadrenergic noncholinergic (NANC) relaxatio ns were frequency-dependent (1 to 32 Hz) and inhibited by either tetro dotoxin or N-W-nitro-L-arginine (L-NNA, 100 mu M). The selective cAMP- specific phosphodiesterase (PDE) type IV inhibitors rolipram (3 mu M) and Ho 20-1724 (3 mu M) significantly potentiated NANC relaxations at each frequency of stimulation. The selective cGMP-specific PDE type V inhibitor zaprinast (3 mu M) failed to significantly alter the maximal NANC response, but it caused a slight potentiation of the response at lower frequencies. The adenylyl cyclase stimulant forskolin, the nitr ic oxide donor compound 3-morpholinosydnonimine (SIN-1), and the guany lyl cyclase stimulant sodium nitroprusside caused concentration-depend ent relaxation of histamine-contracted airway smooth muscle. Rolipram significantly potentiated the relaxation elicited by forskolin. Rolipr am also potentiated responses to SIN-1 and sodium nitroprusside. Consi dered together these data support the hypothesis that cAMP plays a fac ilitory role in NANC relaxation of the human bronchi.