Effects of 5-nitro-2-(3-phenylpropylamino) benzoic acid, anthracene-9-carboxylate, and zaprinast on endothelin-1-induced contractions of pregnant rat myometrium.
OBJECTIVE
The effects of 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), anthracene-9-carboxylate (9-AC) (chloride channel blockers) and zaprinast (an inhibitor of phosphodiesterase-5) on endothelin-1 (ET-1) induced contractions of pregnant rat myometrium were investigated in vitro.


METHODS
Isolated myometrial strips were obtained from pregnant rats, and the strips were mounted in organ baths for recording of isometric tension (n=8). The effects of 10(-7) to 10(-4)M NPPB, 10(-7) to 10(-4)M 9-AC, and 10(-7) to 10(-4)M zaprinast on 10(-8)M ET-1-induced contractions of pregnant rat myometrial smooth muscle were recorded.


RESULTS
NPPB and 9-AC increased the amplitude of ET-1-induced myometrial contractions, while decreasing the frequency, in a concentration-dependent manner. The amplitude of myometrial contractions were significantly increased by NPPB and 9-AC beginning from the concentration of 10(-6)M. The frequency of myometrial contractions were significantly decreased by NPPB and 9-AC beginning from the concentration of 10(-6)M. Zaprinast inhibited the amplitude and frequency of ET-1-induced myometrial contractions in a concentration-dependent manner. Zaprinast-induced decreases in amplitude and frequency of myometrial contractions reached statistical significance beginning from the concentrations of 10(-7)M and 10(-5)M, respectively.


CONCLUSIONS
These data provide evidence that the ET-1-induced contractions of pregnant rat myometrial strips may be modulated by chloride channels. In addition, zaprinast effectively inhibited ET-1-induced contractions in pregnant rat myometrium.
Kaya
Tijen
T
Department of Pharmacology, Cumhuriyet University School of Medicine, Sivas, Turkey.
Guvenal
Tevfik
T
Karadas
Baris
B
Cetin
Ali
A
Soydan
Ahmet Serdar
AS
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D009215:Myometrium / Q000187:drug effects / Q000502:physiology*; D009579:Nitrobenzoates / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases; D011247:Pregnancy; D011688:Purinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014590:Uterine Contraction / Q000187:drug effects*
D000873:Anthracenes; D018118:Chloride Channels; D019332:Endothelin-1; D009579:Nitrobenzoates; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; C010030:9-anthroic acid; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517384:Pde5a protein, rat; C011145:zaprinast; D002118:Calcium