Objective: We studied fetal endothelial function in a model of preeclampsia induced by Nomega-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 microM acetylcholine (ACh) and 1 microM sodium nitroprusside (SNP), respectively, after precontraction with 3 microM prostaglandin F2alpha. 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 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 microM 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.