CALCITONIN-GENE-RELATED PEPTIDE REVERSES THE HYPERTENSION AND SIGNIFICANTLY DECREASES THE FETAL MORTALITY IN PREECLAMPSIA RATS INDUCED BY N-G-NITRO-L-ARGININE METHYL-ESTER

We recently established that the chronic inhibition of nitric oxide pr oduction with N-G-nitro-L-arginine methyl ester (L-NAME) increases blo od pressure and fetal mortality in pregnant rats, Using this animal mo del, we have investigated whether calcitonin gene-related peptide (CGR P) can reverse the pre-eclampsia-like conditions produced by L-NAME, C GRP and L-NAME were chronically infused s.c. into pregnant rats separa tely or together starting on day 17 of gestation; a control group was given saline infusions, Systolic blood pressure was measured on gestat ional days 17, 18, 19 and 22 and post-partum days 1 and 2, The weight and mortality of the pups were recorded immediately after spontaneous delivery, Animals treated with L-NAME exhibited significant elevations of blood pressure on days 18, 19 and 22 of gestation and during post- partum, increased pup mortality (18.4 versus 0.0%) and decreased pup w eights (5.14 +/- 0.07 versus 6.20 +/- 0.06 g), The co-administration o f L-NAME and CGRP prevented the gestational (not the post-partum) L-NA ME hypertension and decreased pup mortality to 6.4% but did not revers e the decreased fetal weight (5.31 +/- 0.06 g), Our data indicate that CGRP (i) participates in regulation of the vascular adaptations that occur during normal pregnancy, (ii) has beneficial effects on the hype rtension and increased mortality of experimental preeclampsia, and (ii i) may exert differential effects on the systemic (i.e, maternal) and fetal components of uteroplacental circulation. These findings may hav e important clinical implications.