Effects of nitric oxide donors on the contractility and prostaglandin synthesis of myometrial strips from pregnant and non-pregnant women.
Nitric oxide (NO) is a potent relaxant of smooth muscle and possibly plays a role in maintaining uterine quiescence during pregnancy. Clinical studies have shown beneficial effects of the stable NO donor glyceryl trinitrate (GTN) for the inhibition of pathological myometrial contractility that occurs in preterm labor or dysmenorrhea. Since there are contradictory results regarding the mediation of the relaxing effect of NO, the myometrial prostaglandin synthesis during superfusion with NO donors was studied. Human myometrial strips obtained either at term Cesarean sections before the onset of labor or after hysterectomies in premenopausal women were studied in a superfusion system. After the manifestation of spontaneous contractions, GTN was added in low doses comparable with in vivo levels (0.4-40 nM) and the effect on myometrial activity, intracellular cGMP and prostaglandin production was analyzed. Additionally, the effect of sodium nitroprusside (SNP)--which releases NO spontaneously--was compared with that of GTN. GTN caused a significant decrease in the contraction frequency of myometrial strips from both pregnant and non-pregnant women similar to that of SNP. There was no significant change in the myometrial synthesis of PGI2, PGF2 alpha and PGE2, whereas the intracellular cGMP content was increased. In conclusion, GTN showed a significant inhibitory effect on human myometrium in vitro in very low doses and therefore represents an interesting therapeutic alternative for the treatment of preterm labor and dysmenorrhea. GTN in low doses did not alter the prostaglandin synthesis of human myometrium.
Wetzka
B
B
Department of Obstetrics, Endocrinology and Reproductive Medicine, Universitätsfrauenklinik Freiburg, Freiburg, Germany.
Schäfer
W R
WR
Stehmans
A
A
Zahradnik
H P
HP
D006152:Cyclic GMP / Q000378:metabolism*; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D006801:Humans; D009215:Myometrium / Q000187:drug effects*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis*; D014590:Uterine Contraction / Q000187:drug effects*
D020030:Nitric Oxide Donors; D011453:Prostaglandins; D009599:Nitroprusside; D015237:Dinoprost; D011464:Epoprostenol; D005996:Nitroglycerin; D006152:Cyclic GMP; D015232:Dinoprostone