Ameliorative effect of apelin-13 against renal complications in L-NAME-induced preeclampsia in rats

Abstract

Pre-eclampsia (PE) accompanying acute liver and kidney injury has remained a master cause of both fetal and maternal mortality and morbidity. Vasoactive mediators, oxidative stress and inflammatory imbalanceshave an important role in PE pathogenesis. Apelin is an adipokine that improves endothelial dysfunction; has anti-inflammatory and antioxidant effects; moreover, its level reduced during PE. This study aimed to explore the effects of apelin-13 administration on preeclampsia-associated renal dysfunction and proteinuria. Thirty-three pregnant female rats were divided into three groups; group: 1 (normal pregnant rats), group: 2 (preeclamptic rats); where rats were injected subcutaneously with 75 mg L-NAME/ kg body weight/day beginning from 9th to 20th day of pregnancy andgroup 3 (apelin-13 treated preeclamptic rats); In which L-NAME-induced preeclamptic rats were subcutaneously injected with 6 × 10−8 mol apelin-13/kg body weight/twice daily starting from 6th to 20th day of pregnancy. In all groups, mean arterial blood pressure, total urine protein, serum urea, creatinine, nitric oxide (NO), endothelin-1 (ET-1), interleukin–6 (IL-6) and malondialdhyde (MDA) were measured. Histopathological examination of kidney tissues was also done. preeclamptic rats showed significantly increased mean arterial blood pressure, total urine proteins, serum urea, creatinine, ET-1, IL-6, and MDA, but revealed a significantly decreased serum NO level. On the other hand, apelin treatment significantly improved these parameters together with amelioration of kidney histoarchitecture in the treated group. In conclusion, apelin may be a potentially curative candidate for prohibiting kidney damage and have a therapeutic benefit in PE rat models.

Intrauterine L-NAME Exposure Weakens the Development of Sympathetic Innervation and Induces the Remodeling of Arterial Vessels in Two-Week-Old Rats

“…We showed that the body weight gain in dams was not affected by the administration of L-NAME from GD10 until a delivery. Notably, L-NAME treatment was able to cause a rise in systolic blood pressure in dams, even though the dose used in this experiment was relatively lower than that reported in the literature [25,26,[34][35][36][37]. A number of studies have shown that a similar effect of L-NAME is observed at higher doses [25][26][27].…”

Intrauterine Nitric Oxide Deficiency Weakens Differentiation of Vascular Smooth Muscle in Newborn Rats

“…Probably, on the 15th day of pregnancy, vascular resistance in L-NAME-treated dams was increased as well, but its contribution to BP level was counterbalanced by the fall in the cardiac output, as seen from lower heart rate values. Of note, the treatment of animals with L-NAME is a commonly used model of preeclampsia [ 16 , 17 ]. In our model, we observed such manifestations of preeclampsia as increased blood pressure level and attenuated NO bioavailability [ 18 , 19 , 20 ].…”

Apelin, APJ, and ELABELA: Role in Placental Function, Pregnancy, and Foetal Development—An Overview

“…In another study, researchers showed that the administration of pyr-apelin-13 at 2 mg/kg body weight/day reduced blood pressure and normalised the heart rate in a rat PE model compared with controls, and also normalised proteinuria in association with lower renal cortical collagen deposition [ 145 ]. Moreover, apelin ameliorated kidney damage in a PE rat model; hence, it might represent a curative candidate for prohibiting kidney damage [ 146 ].…”