Nitroprusside stimulates contractility and the synthesis of 14C-acetylated PAF-like substances in estrogen primed-mouse uterine horns.
We investigated the effect of sodium nitroprusside (SNP), a donor of nitric oxide, on the formation of platelet-activating factor (PAF) and uterine contractility in mouse uterine horns from mice treated with estrogen. Because the major pathway of PAF synthesis is the remodeling pathway in uterine tissue, we evaluated the incorporation of 14C-acetate into PAF-like molecules. Our results showed that SNP (100-300 mumol/L) caused a transient increase in the synthesis of PAF, which remained cell-associated. The addition of SNP (100-300 mumol/L) to a mouse uterine horn in an isolated organ bath preparation evoked a transient increase in contractility, which was inhibited by hemoglobin (2 micrograms/mL), a nitric oxide scavenger, but not by methylene blue (10 mumol/L), a guanylate cyclase inhibitor. The pharmacological characteristics of the contractions evoked by SNP resembled those evoked after mast cell activation, in that they were blocked by ritodrine (a beta 2 adrenergic agonist, 0.1 mumol/L); indomethacin (a cyclooxygenase inhibitor, 10 mumol/L); ketotifen (a mast cell stabilizer, 1.0 mumol/L); cromolyn sodium (a mast cell stabilizer, 100 mumol/L); pyrilamine (an H1 antagonist, 10 mumol/L); and ketanserine (5HT2 antagonist, 0.1 mumol/L). These data demonstrate that nitric oxide generated from SNP stimulated the synthesis of PAF and evoked contractility in uterine horns from mice treated with estrogen. This result suggests the possibility that these tissue conditions might be favorable for the generation of peroxynitrites, possible mediators of both effects. It is also shown that the contractility evoked by the addition of SNP was not due to production of PAF, because its antagonist, WEB 2086 (10-30 mumol/L, a concentration that blocked contractions evoked by PAF 1 nmol/L), had no effect on the SNP-evoked contractions.
Martínez
L
L
Universidad de Concepción, Chile.
Gimeno
M F
MF
Villán
L
L
Villar
M
M
Rudolph
M I
MI
D000818:Animals; D002250:Carbon Radioisotopes; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000096:biosynthesis*; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D002250:Carbon Radioisotopes; D004967:Estrogens; D020030:Nitric Oxide Donors; D010972:Platelet Activating Factor; D009599:Nitroprusside