Effects of atrial natriuretic peptide and 8-brom cyclic guanosine monophosphate on human tracheal smooth muscle.
The relaxant effects of intracellular concentration of cyclic guanosine monophosphate (cGMP) on spontaneous tone in human tracheal smooth muscle were investigated in comparison with guinea pig, using isometric tension records. In both human and guinea pig tracheas, application of atrial natriuretic peptide (ANP) and 8-brom cGMP (a membrane permeable analogue of cGMP) caused an inhibition of spontaneous tone in a concentration-dependent fashion. However, ANP was less potent in relaxation of tracheal smooth muscle in human than guinea pigs, and values of % relaxation induced by 1 mmol/l ANP in human and guinea pigs were 37.1 +/- 5.3 and 82.7 +/- 10.5%, respectively (n = 6). In the presence of 30 nmol/l iberiotoxin (IbTX), a potent and selective large conductance Ca(2+)-activated K+ (BKCa) channel inhibitor, relaxant actions of ANP on human tracheal smooth muscle were markedly suppressed, and values of % relaxation by 1 mmol/l ANP decreased to 8.4 +/- 1.2% (n = 6). On the other hand, 8-brom cGMP was roughly equipotent in relaxating tracheal smooth muscle in these two species, different from ANP, and inhibitory effects of 8-brom cGMP on both human and guinea pig tracheal smooth muscle were also markedly suppressed in the presence of 30 nmol/l IbTX, similar to ANP. These results demonstrate that augmentation of BKCa channel activity may play a functionally important role in the cGMP-induced relaxation in human airway smooth muscle. However, ANP may have modest potency as a bronchodilator.
Mikawa
K
K
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Kume
H
H
Takagi
K
K
D000368:Aged; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects; D024681:Potassium Channels, Calcium-Activated; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; C016276:8-bromocyclic GMP; C064719:iberiotoxin; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP