ABSTRACT
OBJECTIVE: Pre-eclamptic toxemia (PET) affects 4 to 8% of human pregnancies. Presently, reliable specific therapies to treat this disorder are not available. This study was designed to develop a new therapeutic approach in the management of PET using an animal model. DESIGN: Pregnant rats (5/group) infused with 50 mg L-NAME daily via osmotic mini pumps from day 17 of gestation developed a PET-like syndrome. Systolic blood pressure (BP) was monitored daily during pregnancy and up to 7 days postpartum by the tail cuff method. Pup weight and mortality were recorded immediately after delivery. We examined the effect of CGRP to ameliorate L-NAME-induced hypertension during pregnancy, and the efficacy of CGRP and progesterone in combination to inhibit L-NAME-induced hypertension during the post-partum period. RESULTS: Blood pressure in L-NAME-treated rats was significantly elevated (P < 0.01) throughout pregnancy (141 +/- 3 to 166 +/- 10 mm Hg). CGRP 10 micrograms/day did not cause hypotension, the values being similar to controls which received only saline. On the other hand, CGRP infusion inhibited L-NAME-induced hypertension to normotensive levels (116 +/- 3 to 122 +/- 2) during pregnancy (up to day 22 of gestation), but not during postpartum period (137 +/- 8 to 148 +/- 2). During the post-partum period, neither progesterone nor CGRP by itself was effective in lowering L-NAME-induced hypertension. The combination of CGRP with progesterone decreased BP to control levels in the post-partum period, and also significantly improved foetal mortality and growth (P < 0.05). CONCLUSIONS: CGRP inhibited L-NAME-induced hypertension during pregnancy and not during postpartum period. The same phenomenon was evident in the presence of adequate levels of progesterone in the post-partum period. We believe that CGRP regulates vascular adaptations during pregnancy and these effects may be progesterone-dependent. This combination treatment of CGRP plus progesterone may be a promising therapy in the management of PET in humans.