Calcitonin gene-related peptide reverses the hypertension and significantly decreases the fetal mortality in pre-eclampsia rats induced by NG-nitro-L-arginine methyl ester

Abstract

We recently established that the chronic inhibition of nitric oxide production with N(G)-nitro-L-arginine methyl ester (L-NAME) increases blood pressure and fetal mortality in pregnant rats. Using this animal model, we have investigated whether calcitonin gene-related peptide (CGRP) can reverse the pre-eclampsia-like conditions produced by L-NAME. CGRP and L-NAME were chronically infused s.c. into pregnant rats separately or together starting on day 17 of gestation; a control group was given saline infusions. Systolic blood pressure was measured on gestational 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 weights (5.14 +/- 0.07 versus 6.20 +/- 0.06 g). The co-administration of L-NAME and CGRP prevented the gestational (not the post-partum) L-NAME hypertension and decreased pup mortality to 6.4% but did not reverse the decreased fetal weight (5.31 +/- 0.06 g). Our data indicate the CGRP (i) participates in regulation of the vascular adaptations that occur during normal pregnancy, (ii) has beneficial effects on the hypertension and increased mortality of experimental preeclampsia, and (iii) may exert differential effects on the systemic (i.e. maternal) and fetal components of utero-placental circulation. These findings may have important clinical implications.