Prr. Gangula et al., CALCITONIN-GENE-RELATED PEPTIDE IS A DEPRESSOR IN N-G-NITRO-L-ARGININE METHYL ESTER-INDUCED HYPERTENSION DURING PREGNANCY, Hypertension, 29(1), 1997, pp. 248-253
Inhibition of nitric oxide production with N-G-nitro-L-arginine methyl
ester (L-NAME) increases blood pressure and fetal mortality in pregna
nt rats. We previously reported that administration of calcitonin gene
-related peptide (CGRP) reduces the blood pressure and fetal death pro
duced by L-NAME. To determine the hemodynamic role of endogenous CGRP
in this setting, CGRP(8-37), a CGRP receptor antagonist, was used. In
addition, CGRP mRNA and peptide levels were determined in dorsal root
ganglia. L-NAME or control rats had intravenous (for drug administrati
on) and arterial (for continuous mean blood pressure monitoring) cathe
ters surgically placed and were studied in the conscious unrestrained
state. Baseline blood pressure was higher in the L-NAME than the contr
ol rats on days 19, 20, and 21 or pregnancy and postpartum day 1. Vehi
cle administration did not change blood pressure in any group, and CGR
P(8-37) (100 mu g) did not change blood pressure in control groups. Ho
wever, CGRP(8-37) administration to the L-NAME rats further increased
blood pressure (P<.05) on days 19 (8+/-1), 20 (12+/-2), and 21 (7+/-1)
of gestation but was without effect on postpartum day 1. Furthermore,
CGRP mRNA or peptide levels in dorsal root ganglia were not different
between the L-NAME and control rats at any of the time points studied
. These data indicate that in experimental preeclampsia, CGRP is playi
ng a compensatory vasodilator role to attenuate the elevated blood pre
ssure. The mechanism of this effect appears to be an enhanced vascular
responsiveness to CGRP that is attenuated after the birth of pups.