Effects of endothelin-1 and calcium channel blockers on contractions in human myometrium. A study on myometrial strips from normal and diabetic pregnant women.
OBJECTIVE
We studied the effect of endothelin (ET)-1 on spontaneous contractions and the effects of nimodipine and isradipine on ET-1-induced contractions in myometrial tissue from normal and diabetic pregnant women.


METHODS
We isolated myometrial strips from seven normal pregnant and seven gestational diabetic women undergoing elective cesarean section at term. Three sets of experimental studies were performed with three myometrial strips obtained from every woman and mounted in organ baths for recording of isometric tension. In the first set, the effect of increasing concentrations of ET-1 (10(-11)-10(-8) M) on spontaneous contractions was recorded. In the second and third sets, effects of increasing concentration of nimodipine (10(-6)-3.10(-5) M) and isradipine (10(-5)-3.10(-4) M), respectively, on contractions following pretreatment with 10(-8) M ET-1 were recorded.


RESULTS
ET-1, beginning from 10(-9) M and 10(-10) M, significantly increased the amplitude of contractions in normal and diabetic strips, respectively. ET-1, beginning from 10(-9) M, also increased the frequency of contractions in normal and diabetic strips. The amplitude of contractions was significantly higher in diabetic strips as compared with normal strips at 10(-9) and 10(-8) M. There was no significant difference in the frequency of contractions between normal and diabetic strips. ET-1 at 10(-8) M also increased the basal tone of all normal and diabetic strips. Nimodipine, beginning from 10(-6) M and 3.10(-6) M, and isradipine, beginning from 10(-5) M and 3.10(-5) M, significantly decreased the amplitude of contractions in normal and diabetic strips, respectively. Nimodipine at 10(-5) M and 3.10(-5) M and isradipine at 3.10(-4) M significantly decreased the frequency of contractions in normal strips. Nimodipine, except at 3.10(-5) M, and isradipine did not significantly decrease the frequency of contractions in diabetic strips.


CONCLUSIONS
Gestational diabetes increases ET-1-induced contractile response in human myometrium. The contractile effect of ET-1 in normal and diabetic myometrium is mediated partly by dihydropyridine-sensitive calcium channels since it is significantly reduced by nimodipine and isradipine. The promising data from this study warrant clinical studies on the definitive place of nimodipine and isradipine in the treatment of preterm labor, especially in a diabetic woman, to avoid metabolic complications of beta-mimetic tocolytics.
Kaya
T
T
Department of Pharmacology, Cumhuriyet University School of Medicine, Sivas, Turkey. cetin@turnet.net.tr
Cetin
A
A
Cetin
M
M
Sarioglu
Y
Y
D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D016640:Diabetes, Gestational / Q000503:physiopathology*; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D006801:Humans; D017275:Isradipine / Q000494:pharmacology / Q000627:therapeutic use; D009215:Myometrium / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D009553:Nimodipine / Q000494:pharmacology / Q000627:therapeutic use; D007752:Obstetric Labor, Premature / Q000188:drug therapy; D011247:Pregnancy / Q000502:physiology*; D012016:Reference Values; D014590:Uterine Contraction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D019332:Endothelin-1; D009553:Nimodipine; D017275:Isradipine