Interaction between nitric oxide and prostaglandin E2 pathways in pregnant rat uteri

We examined the possible interrelationship between nitric oxide (NO) and cyclooxygenase (COX) products in the uterus during pregnancy and labor. Results indicate that 1) rat uteri during labor, at term, demonstrated a 69% decrease in nitrite production and a 217% increase in prostaglandin E2 (PGE2) production compared with day 18 of pregnancy; 2) interleukin-1 beta (IL-1 beta) induced a pronounced elevation of both nitrites and PGE2 in rat uteri; 3) diethylenetriamine/NO, a donor of NO, induced a significant increase of PGE2 production by the uterus in a dose-dependent manner; 4) NG-nitro-L-arginine methyl ester, an inhibitor of NO synthesis, markedly inhibited IL-1 beta-induced nitrite and PGE2 in rat uteri; this inhibitory action was reversed by coincubation with L-arginine; 5)exogenous PGE2 significantly inhibited IL-1 beta-induced, but not constitutive, nitrite production; and 6) inhibition of endogenous PGE2 by indomethacin substantially increased IL-1 beta-induced nitrite production. Thus the interaction between NO and COX pathways might be important in the regulation of uterine contractility during pregnancy and labor.