PRE-ECLAMPSIA-LIKE CONDITIONS PRODUCED BY NITRIC-OXIDE INHIBITION - EFFECTS OF L-ARGININE, D-ARGININE AND STEROID-HORMONES

The aim of this study was to establish that inhibiting nitric oxide (N O) production with N-G-nitro-L-arginine methyl ester (L-NAME) results in high blood pressure conditions in chronically treated pregnant rats , To validate the model, the effects of L-arginine (the substrate for NO) and D-arginine (the stereoisomer of L-arginine which is not a subs trate for NO synthesis) were studied on blood pressure and fetal weigh ts, The effects of a progesterone agonist, promegestone (R5020) and 17 beta-oestradiol were also explored, The NO synthase inhibitor L-NAME was chronically infused s.c. into pregnant rats from day 17 of gestati on, either alone or with the simultaneous infusion of L-arginine and i njections of sex steroid hormones (promegestone and oestradiol), compo unds that may act in the pathogenic pathways of pre-eclampsia, Systoli c blood pressure was measured daily, Weight and mortality of pups were recorded immediately after delivery, Blood pressure was elevated sign ificantly in rats treated with L-NAME for only 1 day following infusio n; there was a consistent decline during the next 3 days of pregnancy followed by a dramatic and significant rise just prior to delivery and post-partum, Fetal weights were reduced significantly in the L-NAME-t reated rats, Go-treatment of L-NAME-infused rats with L-arginine rever sed both the increase in blood pressure and the decrease in fetal weig hts observed with L-NAME alone, R5020, but not oestradiol, also reduce d blood pressure and increased fetal weights in the L-NAME-treated ani mals, NO appears to play essential roles in the regulation of blood pr essure during pregnancy, as well as in fetal perfusion and fetal weigh ts at delivery, This study also indicates that progesterone, and not o estrogen, may regulate the vascular adaptations during normal pregnanc y, L-Arginine and progesterone agonists like promegestone may have ben eficial effects on the high blood pressure levels and reduced fetal we ights associated with pre-eclampsia.