Nitric oxide in the contractile action of bradykinin, oxytocin, and prostaglandin F2 a in the estrogenized rat uterus

CHAUD MARCELA; FRANCHI ANA MARIA; RETTORI, VALERIA; MCCANN SAMUEL; GIMENO MARTA

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Lugar: Washington DC, USA; Año: 1997 vol. 94 p. 11049 - 11054

0027-8424

Experiments were performed on uteri fromestrogen-primed female rats. Bradykinin (BK) (1028 M)significantly augmented biosynthesis of prostaglandin F2 a(PGF2a) and prostaglandin E2 (PGE2), and this synthesis wascompletely blocked by NG-monomethyl L-arginine (NMMA)(300 mM), a competitive inhibitor of nitric oxide synthase(NOS). Blockade of prostaglandin synthesis by indomethacincaused rapid dissipation of isometric developed tension (IDT)induced by BK. Blockade of NOS with NMMA had similar butless marked effects. Combining the two inhibitors produced aneven more rapid decay in IDT, suggesting that BK-induced NOrelease maintains IDT by release of prostanoids. The declineof frequency of contraction (FC) was not significantly alteredby either indomethacin or NMMA but was markedly acceleratedby combination of the inhibitors, which suggests that PGsmaintain FC and therefore FC decline is accelerated onlywhen PG production is blocked completely by combination ofthe two inhibitors of PG synthesis. The increase in IDTinduced by oxytocin was unaltered by indomethacin, NMMAor their combination indicating that neither NO nor PGs areinvolved in the contractions induced by oxytocin. However, thedecline in FC with time was significantly reduced by theinhibitor of NOS, NMMA, suggesting that FC decay followingoxytocin is caused by NO released by the contractile process.In the case of PGF2a,NMMA resulted in increased initial IDTand FC. The decline in FC was rapid and dramaticallyinhibited by NMMA. Receptor-mediated contraction by BK,oxytocin, and PGF2a is modulated by NO that maintains IDTby releasing PGs but reduces IDT and FC via cyclic GMP.