NITRIC-OXIDE IN THE CONTRACTILE ACTION OF BRADYKININ, OXYTOCIN, AND PROSTAGLANDIN-F-2-ALPHA IN THE ESTROGENIZED RAT UTERUS

Experiments were performed on uteri from estrogen-primed female rats, Bradykinin (BK) (10(-8) M) significantly augmented biosynthesis of pro staglandin F-2 alpha (PGF(2) alpha) and prostaglandin E-2 (PGE(2)), an d this synthesis was completely blocked by N-G-monomethyl L-arginine ( NMMA) (300 mu M), a competitive inhibitor of nitric oxide synthase (NO S), Blockade of prostaglandin synthesis by indomethacin caused rapid d issipation of isometric developed tension (IDT) induced by BK, Blockad e of NOS with NMMA had similar but less marked effects, Combining the two inhibitors produced an even more rapid decay in IDT, suggesting th at BK-induced NO release maintains IDT by release of prostanoids, The decline of frequency of contraction (FC) was not significantly altered by either indomethacin or NMMA but was markedly accelerated by combin ation of the inhibitors, which suggests that PGs maintain FC and there fore FC decline is accelerated only when PG production is blocked comp letely by combination of the two inhibitors of PG synthesis, The incre ase in IDT induced by oxytocin was unaltered by indomethacin, NMMA or their combination indicating that neither NO nor PGs are involved in t he contractions induced by oxytocin, However, the decline in FC with t ime was significantly reduced by the inhibitor of NOS, NMMA, suggestin g that FC decay following oxytocin is caused by NO released by the con tractile process, In the case of PGF(2) alpha, NMMA resulted in increa sed initial IDT and FC, The decline in FC was rapid and dramatically i nhibited by NMMA, Receptor-mediated contraction by BK, oxytocin, and P GF(2) alpha is modulated by NO that maintains IDT by releasing PGs but reduces IDT and FC via cyclic GMP.