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

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Abstract

Objective

We studied fetal endothelial function in a model of preeclampsia induced by Nω-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 F2α. The role of nitric oxide in ACh relaxation was assessed by incubation with 0.1 mM NG-monomethyl-l-arginine (L-NMMA) or 0.1 mM l-arginine (l-Arg). Precontraction with 50 mM potassium 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 impairment 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.

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Authors and Affiliations

  1. Area de Pediatría y Neonatología, Fundación Hospital Alcorcón, Spain

    José Martínez-Orgado MD, PhD, Rita González, María J. Alonso PhD & Mercedes Salaices PhD

  2. Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain

    José Martínez-Orgado MD, PhD, Rita González, María J. Alonso PhD & Mercedes Salaices PhD

Authors
  1. José Martínez-Orgado MD, PhD
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  2. Rita González
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  3. María J. Alonso PhD
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  4. Mercedes Salaices PhD
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Corresponding author

Correspondence to José Martínez-Orgado MD, PhD.

Additional information

Supported by grants from D.G.I.C.Y.T. (BXX-2000-0153), and FISS (P1021540).

The authors thank the vererinarian Dr. María del Carmen Fernández-Criado for the care of animals, Fernando Nuñez and Lourdes Hernández for their excellent technical assistance, and Ms. Carol Warren for her linguistic assistance.

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Martínez-Orgado, J., González, R., Alonso, M.J. et al. Impairment of Fetal Endothelium-Dependent Relaxation in a Rat Model of Preeclampsia by Chronic Nitric Oxide Synthase Inhibition. Reprod. Sci. 11, 82–88 (2004). https://doi.org/10.1016/j.jsgi.2003.08.003

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