Mechanism of atrial natriuretic polypeptide and sodium nitroprusside-induced relaxation in guinea-pig tracheal smooth muscle.
Atrial natriuretic polypeptide (ANP) is composed of a family of peptides isolated from rat and human atria. In the present study, the relaxant effects of ANP, sodium nitroprusside and 8-bromo-cyclic guanosine monophosphate (GMP) were investigated in guinea-pig tracheal smooth muscle, and the tissue cyclic GMP and cyclic adenosine monophosphate (AMP) concentrations were measured. ANP, sodium nitroprusside and 8-bromo-cyclic GMP showed relaxant effects on the spontaneous tone in normal Krebs solution (5.9 mmol/l K(+)-2.4 mmol/l Ca++ solution). They diminished relaxant effects on 40 mmol/l K(+)-0.1 mmol/l Ca++ induced contraction, which was approximately the same tension as the spontaneous tone. Sodium nitroprusside and 8-bromo-cyclic GMP diminished less relaxant effects on 40 mmol/l K(+)-2.4 mmol/l Ca++ induced contraction, but ANP showed no relaxation. The tissue cyclic GMP levels following administration of ANP and sodium nitroprusside in normal Krebs solution, in 40 mmol/l K(+)-2.4 mmol/l Ca++ solution, and in 40 mmol/l K(+)-0.1 mmol/l Ca++ solution increased dose-dependently without regard to external Ca++ concentrations, while the tissue cyclic AMP levels did not change. These results suggest that ANP might be a novel potent relaxant in airway smooth muscle and the relaxant effect may be, at least in part, mediated by cyclic GMP. There was a difference in relaxant effects on tracheal smooth muscle between ANP and sodium nitroprusside.
Watanabe
H
H
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Suzuki
K
K
Takagi
K
K
Satake
T
T
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects
D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002118:Calcium