Lb. Fernandes et al., POTENTIATION OF NONADRENERGIC NONCHOLINERGIC RELAXATION OF HUMAN ISOLATED BRONCHUS BY SELECTIVE INHIBITORS OF PHOSPHODIESTERASE ISOZYMES, American journal of respiratory and critical care medicine, 150(5), 1994, pp. 1384-1390
Citations number
15
Categorie Soggetti
Emergency Medicine & Critical Care","Respiratory System
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.