Nitric oxide in the contractile action of bradykinin, oxytocin, and prostaglandin F2 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 prostaglandin F2 alpha (PGF2alpha) and prostaglandin E2 (PGE2), and this synthesis was completely blocked by NG-monomethyl L-arginine (NMMA) (300 microM), a competitive inhibitor of nitric oxide synthase (NOS). Blockade of prostaglandin synthesis by indomethacin caused rapid dissipation of isometric developed tension (IDT) induced by BK. Blockade of NOS with NMMA had similar but less marked effects. Combining the two inhibitors produced an even more rapid decay in IDT, suggesting that 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 combination of the inhibitors, which suggests that PGs maintain FC and therefore FC decline is accelerated only when PG production is blocked completely by combination of the two inhibitors of PG synthesis. The increase in IDT induced by oxytocin was unaltered by indomethacin, NMMA or their combination indicating that neither NO nor PGs are involved in the contractions induced by oxytocin. However, the decline in FC with time was significantly reduced by the inhibitor of NOS, NMMA, suggesting that FC decay following oxytocin is caused by NO released by the contractile process. In the case of PGF2alpha, NMMA resulted in increased initial IDT and FC. The decline in FC was rapid and dramatically inhibited by NMMA. Receptor-mediated contraction by BK, oxytocin, and PGF2alpha is modulated by NO that maintains IDT by releasing PGs but reduces IDT and FC via cyclic GMP.
Chaud
M
M
Centro de Estudios Farmacologicos y Botanicos, Consejo Nacional de Investigaciones Cientificos y Tecnicas, Serrano 669,1414, Buenos Aires, Argentina.
Franchi
A M
AM
Rettori
V
V
McCann
S M
SM
Gimeno
M F
MF
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010121:Oxytocin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology
D004967:Estrogens; D009569:Nitric Oxide; D010121:Oxytocin; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D001920:Bradykinin