Adrenomedullin Requires an Intact Nitric Oxide System to Function as an Endogenous Vasodilator in Rat Gestation

Abstract

Objective: We hypothesize that administration of adrenomedullin (AM), an endogenous vasodilator, will ameliorate the hypertension and growth restriction associated with chronic nitric oxide inhibition induced by l‐ω nitro‐l‐arginine methyl ester (l‐NAME) infusion in pregnant rats. Methods. Osmotic minipumps were inserted on day 14 of gestation to deliver continuously either AM, l‐NAME, AM+l‐NAME, or vehicle control. Systolic blood pressure was recorded daily in pregnant rats. Pregnant rats were either sacrificed on gestational days 15, 16, 17, 18, or 22, or they were allowed to deliver at term. The placentas from all of the treated groups were fixed for 24 hr in Bouin solution, sectioned, processed, embedded in paraffin, and stained with hematoxylin and eosin. The placentas were graded for the quality of fetal vessel development in the labyrinth. Results. Systolic blood pressure was increased in AM+l‐NAME‐treated rats. The animals that delivered in the AM+l‐NAME group exhibited decreased pup weight (l‐NAME and AM+l‐NAME, 5.2±0.1 compared with 6.4±0.1 g for both AM and controls, p<0.001) and increased pup mortality (AM+l‐NAME, 44.4% compared with 16.7% in l‐NAME, 0% in AM and 3.1% in controls, p<0.001 AM+l‐NAME compared with controls). Increased decidual necrosis, necrosis in the labyrinth, and deficient fetal vessel development in the labyrinth was identified in the placentas treated with AM+l‐NAME. Conclusions. Addition of the endogenous vasodilator AM to an l‐NAME‐induced state of chronic NO inhibition did not ameliorate hypertension and growth restriction.