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Impairment of Fetal Endothelium-Dependent Relaxation in a Rat Model of Preeclampsia by Chronic Nitric Oxide Synthase Inhibition

Area de Pediatría y Neonatología, Fundación Hospital Alcorcón; Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; Servicio de Neonatología. Hospital Clínico San Carlos, Martín Lagos, s/n. 28040-Madrid, Spain; josemorg{at}inicia.es

Rita González

María J. Alonso, PhD

Mercedes Salaices, PhD

Area de Pediatría y Neonatología, Fundación Hospital Alcorcón; Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain

Objective: We studied fetal endothelial function in a model of preeclampsia induced by N-nitro-L-arginine methylester (L-NAME) administration in pregnant rats.

Methods: Aortic segments from term fetuses and 2-day-old Wistar rats treated with L-NAME (0.5 mg/mL in drinking water) (fetuses from hypertensive rats, FH, and newborns from hypertensive rats, NH) and from untreated rats (fetuses from normotensive rats, FN, and newborns from normotensive rats, NN) were obtained. Endothelium-dependent and -independent relaxations were determined by the response to 1 µM acetylcholine (ACh) and 1 µM sodium nitroprusside (SNP), respectively, after precontraction with 3 µM prostaglandin F₂. The role of nitric oxide in ACh relaxation was assessed by incubation with 0.1 mM N^G-monomethyl-L-arginine (L-NMMA) or 0.1 mM L-arginine (L-Arg). Precontraction with 50 mM ptoassium chloride assessed the role of hyperpolarizing mechanisms.

Results: In FH, ACh-induced relaxation was reduced (FH 34.2 ± 4%, FN 45.8 ± 2%, P < .05), whereas that of SNP was enhanced (FH 68.4 ± 5%, FN 50.4 ± 4%, P < .05). L-Arg did not reverse the impirment of ACh relaxation. L-NMMA reduced ACh relaxation in FN but increased it in FH; this increase was abolished by potassium chloride precontraction and by 1 µM capsaicine, a calcitonin-gene related peptide inhibitor. The hyperpolarizing component of ACh relaxation was reduced in FH as compared with FN. By contrast, ACh relaxation was greater in NH than in NN, with the relative participation of nitric oxide and hyperpolarizing-related components being similar in both groups.

Conclusion: Fetal ACh relaxation was impaired in this preeclampsia-like model. This impairment is probably not exclusively an effect of L-NAME but could reflect endothelial dysfunction that disappears after birth.

Key Words: Preeclampsia • endothelium • nitric oxide • hyperpolarization • fetus

Journal of the Society for Gynecologic Investigation, Vol. 11, No. 2, 82-88 (2004)
DOI: 10.1016/j.jsgi.2003.08.003


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