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Administration of N-L-Arginine Methyl Ester (L-NAME) Impairs Endothelium-Dependent Relaxation in Gravid But Not Nongravid Rats

Rita González, BS

Silvia Tovar, BS

Jesús Marín, MD, PhD

Mercedes Salaices, PhD

Area de Pediatría y Neonatologí. Foundación Hospital Alcorcón, Madrid, Spain; Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain

María J. Alonso, PhD

Area de Pediatría y Neonatologí. Foundación Hospital Alcorcón, Madrid, Spain; Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo, 4, 28029- Madrid, Spain; mariajesus.alonso{at}uam.es

Objective: To characterize the impariment of endothelium-dependent relaxation induced by administration of the nitric oxide synthase (NOS) inhibitor N-L-arginine methyl ester (L-NAME) to gravid rats and to determine whether L-NAME affects nongravid rats in a similar manner.

Methods: Acetylcholine (ACh; 0.01-10 µM) relaxation was studied in aortic segments (contracted with 10 nM norepinephrine) from Wistar rats that were hypertensive after receiving L-NAME (0.5 mg/mL in drinking wateR) before gravidity (hypertensive virgin rats [HVR]), during gravidity (hypertensive gravid rats [HGR]), or during the last 10 days of gravidity to 24 hours postpartum (hypertensive puerperal rats [HPR]). We also studied aortic segments from corresponding groups of untreated normotensive rats (normotensive gravid rats [NGR], normotensive puerperal rats [NPR], and normotensive virgin rats [NVR]). The approximate participations of NO and the hyperpolarizing mechanisms in ACh relaxation were calculated from the reduction of relaxation observed, respectively, after incubation with the NOS inhibitor N^G-monomethyl-L-arginine (L-NMMA, 0.1 mM) or after contraction with 50 mM of potassium chloride. Expression of endothelial NOS protein was studied by Western blot in segments of HGR and NGR.

Results: Acetylcholine relaxation was reduced in HGR compared with NGR, and this reduction correlated with the severity of hypertension. In contrast, ACh relaxation in HVR was similar to that in NVR, and that of HPR was similar to that in NPR. The NO component of relaxation was reduced in HGR but preserved in the other groups. Nevertheless, there were no differences in endothelial NOS protein expression between NGR and HGR. The hyperpolarizing component in relaxation was enhanced in HVR and HPR but not HGR.

Conclusion: Administration of L-NAME induced an impairment of endothelium-dependent relaxation, involving both nitric oxide- and hyperpolarizing-dependent mechanisms in gravid but not virgin rats; this impairment resolved with delivery.

Key Words: Preeclampsia • L-NAME • endothelium • rats

Journal of the Society for Gynecologic Investigation, Vol. 10, No. 2, 74-81 (2003)
DOI: 10.1016/S1071-55760200220-4


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