Differential responses of mesenteric arterial bed to vasoactive substances in L-NAME-induced preeclampsia: Role of oxidative stress and endothelial dysfunction

Abstract

To investigate the systemic and placental oxidant status as well as vascular function in experimental preeclampsia (PE) induced by nitro-L-arginine methyl ester (L-NAME). Fetal parameters and maternal blood pressure, proteinuria, mesenteric arterial bed (MAB) reactivity, and systemic and placental oxidative stress were compared between four groups: pregnant rats receiving L-NAME (60 mg/kg/day, orally) (P + L-NAME) or vehicle (P) from days 13 to 20 of pregnancy and nonpregnant rats receiving L-NAME (NP + L-NAME) or vehicle (NP) during 7 days. L-NAME administration during pregnancy induced some hallmarks of PE, such as hypertension and proteinuria. The P + L-NAME group presented lower weight gain and placental mass as well as reduced number and weight of live fetuses than P group. The vasodilator effect induced by acetylcholine (ACh) and angiotensin II (Ang II) was lower in the perfused MAB from NP + L-NAME and P + L-NAME than in control groups. Otherwise, the nitroglycerine-induced vasodilation and the phenylephrine- and Ang II-induced vasoconstriction were higher in MAB from NP + L-NAME and P + L-NAME groups than in the respective controls. Systemic and placental oxidative damage, assessed by malondialdehyde and carbonyl levels, was increased and activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were reduced in P + L-NAME and NP + L-NAME groups compared to controls. The present data suggest that the oxidative stress and reduced bioavailability of nitric oxide may contribute to attenuation of vasodilator responses to ACh and Ang II, and hyperreactivity to Ang II in the mesentery of preeclamptic rat, which may contribute to the increased peripheral vascular resistance and BP, as well as intrauterine growth restriction in L-NAME-induced PE.

Serum Adropin Levels in a Preeclampsia Like L-Name Rat Model Treated with Sildenafil Citrate

“…In this study, experimental preeclampsia model induced by L-NAME were successfully established and proved by maternal hypertension, proteinuria, increased serum levels of urea and creatinine, besides decreased placental and fetal weights, these findings were consistent with other reports of Zhou et al, [33] and Amaral et al, [34] . Moreover, the histopathological findings were agreed with Powe et al, [35] .…”

“…In the L-NAME model, the free fatty acid oxidation disorders occur, with decreased levels of mRNA and protein expression of long-chain 3 -hydroxyacyl-CoA dehydrogenase (LCHAD), FFA levels were negatively correlated with LCHAD levels [54]. Oxidative stress has been implicated in the pathophysiology of preeclapmsia because it damages the maternal vascular endothelium as reported by human [34,55,56] and animal studies [57,58] .…”

Evaluation of blood vessel injury, oxidative stress and circulating inflammatory factors in an L‑NAME‑induced preeclampsia‑like rat model

“…Similarly, the plasma levels of MDA in the pregnant rats after L-NAME treatment were substantially increased. As observed in the development of human preeclampsia, L-NAME-treated pregnant rats exhibited oxidative stress, which may be one of the causes of preeclampsia or may lead to more serious premenstrual symptoms ( 40 ). MCP-1 is a secreted single-chain protein and a member of the chemokine family; as one of the major chemokines, MCP-1 induces chemotaxis via the G protein-coupled receptor pathway, as well as macrophage migration and infiltration.…”

Vagus Nerve Stimulation Ameliorates L-NAME-induced Preeclampsia-like Symptoms in Rats Through Inhibition of the Inflammatory Response

“…We also identi ed lower placenta and fetus weights in the L-NAME-treated groups, which concur with published research papers. 33 Partial reversal of growth retardation was observed in the VNS group, where the weight of the fetuses was similar to that of fetuses from the control goup.…”