REGULATION BY NITRIC-OXIDE OF PROSTAGLANDIN-E SYNTHESIS AND SPONTANEOUS MOTILITY IN RAT UTERINE TISSUE

We explored the role of endogenous nitric oxide (NO) in the spontaneou s motility of uterine tissue from pseudopregnant (psp) rats and the co rrelation between this action and the uterotonic prostaglandin (PG) E production. We worked in the early psp (on day 5 of psp), and in late psp (on day 8 and day 9). Treatment with N-G-monomethyl-L-arginine L-N MMA (300 mu M), a competitive nitric oxide synthase (NOS) inhibitor, d id not modify isometric developed tension (IDT) and frequency of contr actions (FC) on day 5 of psp; on day 8, tissue pretreated with L-NMMA showed an increase in the IDT and FC compared with controls, while on day 9 of psp, both IDT and FC showed a lower stability after treatment with the inhibitor. These data suggest that NO modulates uterine moti lity on day 8 (decreasing it) and on day 9 of psp (enhancing it). We a lso evaluated the total NOS activity and that of its isoforms at the t hree times mentioned, demonstrating that total NOS activity was higher on day 5 of psp and decreased with psp development. On day 5 of psp, calcium-dependent and calcium-independent NOS each forms around 50% of total NOS activity. On day 8 of psp, the calcium-dependent was the pr edominant NOS form, while on day 9 of psp, the uterine tissue showed a higher calcium-independent form of the enzyme. In view of the fact th at we found an inhibitor effect of the endogenous NO in uterine contra ctility on day 8 of psp and an inverse action on day 9 of psp (enhanci ng uterine contractility), we suggest that the NOS calcium-dependent f orm could be responsible for uterine contractility in psp rats. Finall y, we evaluated the relationship between endogenous NO and PGE product ion. We observed that on days 5 and 8 of psp, the L-NMMA (300 mu M) tr eatment did not affect PGE production, but on day 9 of psp, the preinc ubation with the NOS inhibitor diminished PGE synthesis, suggesting th at at this time endogenous NO can upregulate uterine PGE production. T hese results confirm that NO can modulate uterine motility by means of PGE production. In summary, we suggest that in uterine tissue from ps p rats, the NO system can alternatively decrease or increase uterine c ontractions, this last effect by enhancing uterine PGE synthesis.