TITLE

Asymmetric Dimethylarginine Is Associated with Developmental Programming of Adult Kidney Disease and Hypertension in Offspring of Streptozotocin-Treated Mothers

AUTHOR(S)
Tain, You-Lin; Lee, Wen-Chin; Hsu, Chien-Ning; Lee, Wei-Chia; Huang, Li-Tung; Lee, Chien-Te; Lin, Ching-Yuang
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Diabetes mellitus complicates pregnancies, leading to diseases in adult life in the offspring. Asymmetric dimethylarginine (ADMA) is increased in diabetes mellitus, kidney disease, and hypertension. We tested whether maternal diabetes causes increased ADMA in rats, resulting in kidney disease and hypertension in the adult offspring, and whether these can be prevented by maternal citrulline supplementation. Newborn female and pregnant Sprague-Dawley rats were injected with streptozotocin (STZ), which made up the nSTZ and STZ models, respectively. For the STZ model, 4 groups of male offspring were killed at age 3 months: the control, STZ, and Cit and STZ+Cit (control and STZ rats treated with 0.25% l-citrulline solution, respectively) groups. The nSTZ rats had lower nephron numbers. The renal level of ADMA was higher in the nSTZ rats than in controls. The STZ group developed kidney injury, renal hypertrophy, and elevated blood pressure at the age of 12 weeks. These conditions were found to be associated with increased ADMA levels, decreased nitric oxide (NO) production, and decreased dimethylarginine dimethylaminohydrolase (DDAH) activity in the kidney. In addition, ADMA caused a nephron deficit in cultured rat metanephroi. Maternal citrulline supplementation prevented hypertension and kidney injury, increased the renal DDAH-2 protein level, and restored the levels of ADMA and NO in the STZ+Cit group. Reduced nephron number and increased ADMA contribute to adult kidney disease and hypertension in offspring of mothers with STZ-induced diabetes. Manipulation of the ADMA-NO pathway by citrulline supplementation may be a potential approach to prevent these conditions.
ACCESSION #
87623749

 

Related Articles

  • Exposure to Maternal Diabetes Induces Salt-Sensitive Hypertension and Impairs Renal Function in Adult Rat Offspring. Nehiri, Touria; Van Huyen, Jean-Paul Duong; Viltard, Mélanie; Fassot, Céline; Heudes, Didier; Freund, Nicole; Deschênes, Georges; Houillier, Pascal; Bruneval, Patrick; Lelièvre-Pégorier, Martine // Diabetes;Aug2008, Vol. 57 Issue 8, p2167 

    OBJECTIVE--Epidemiological and experimental studies have led to the hypothesis of fetal origin of' adult diseases, suggesting that some adult diseases might be determined before birth by altered fetal development. We have previously demonstrated in the rat that in utero exposure to maternal...

  • Impact of High Salt Independent of Blood Pressure on PRMT/ADMA/DDAH Pathway in the Aorta of Dahl Salt-Sensitive Rats. Yu Cao; Jian-Jun Mu; Yuan Fang; Zu-Yi Yuan; Fu-Qiang Liu // International Journal of Molecular Sciences;Apr2013, Vol. 14 Issue 4, p8062 

    Endothelial dysfunction participates in the development and progression of salt-sensitive hypertension. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS). The objectives of this study were to investigate the impact of a high salt diet on the...

  • Renovascular effects of sympathetic cotransmitters ATP and NPY are age-dependent in spontaneoulsy hypertensive rats. Vonend, Oliver; Okonek, Axel; Stegbauer, Johannes; Habbel, Sina; Quack, Ivo; Rump, Lars Christian // Cardiovascular Research;May2005, Vol. 66 Issue 2, p345 

    Abstract: Objective: Hypertension is characterized by sympathetic overactivity. Neuropeptide Y (NPY) and ATP are cotransmitters of norepinephrine (NE) and regulate renovascular resistance. The present study analyzes sympathetic nonadrenergic neurotransmission in hypertensive (SH-SP) and...

  • Apelin-13 deteriorates hypertension in rats after damage of the vascular endothelium by ADMA. Han, Xue; Zhang, Dong-Liang; Yin, Dao-Xin; Zhang, Qi-Dong; Liu, Wen-Hu // Canadian Journal of Physiology & Pharmacology;Sep2013, Vol. 91 Issue 9, p708 

    Asymmetric dimethylarginine (ADMA) is a risk factor for endothelial dysfunction. The polypeptide apelin has biphasic effects on blood vessels in vivo and in vitro. We investigated the effect of apelin-13 on ADMA-damaged vessels. Rats were divided among ADMA-treated and control groups, which were...

  • Brain Ventricular Enlargement in Embryonic, Neonatal and Adulthood Stages of Rats Born from Diabetic Mothers. Maryam, Tehranipour // Journal of Biological Sciences;2008, Vol. 8 Issue 4, p940 

    Structural brain abnormalities are more frequent in diabetes. Cerebrospinal fluid (CSF) is vital in controlling development of the nervous system along the whole length of the neural tube and the externalization of CSF during development is essential for the formation of the layers of neurons in...

  • Microanatomical Study of the Maternal Diabetes Effects on Rat's Choroids Plexus in Embryonic, Neonatal and Adulthood Stages. Tehranipour, M. // Journal of Biological Sciences;2008, Vol. 8 Issue 4, p1199 

    In this research, the effect of maternal diabetes on the choroids plexus volume changes and total length of capillaries in (15°, 1-day-old and 30-day-old) rat neonates was studied. Diabetes was induced by streptozotocin (60 mg kg-1), given by a single intraperitoneal injection to female...

  • T-type calcium channel blockade as a therapeutic strategy against renal injury in rats with subtotal nephrectomy. Sugano, N.; Wakino, S.; Kanda, T.; Tatematsu, S; Homma, K.; Yoshioka, K.; Hasegawa, K.; Hara, Y.; Suetsugu, Y.; Yoshizawa, T.; Utsunomiya, Y.; Tokudome, G.; Hosoya, T.; Saruta, T.; Hayashi, K. // Kidney International;Apr2008, Vol. 73 Issue 7, p826 

    T-type calcium channel blockers have been previously shown to protect glomeruli from hypertension by regulating renal arteriolar tone. To examine whether blockade of these channels has a role in protection against tubulointerstitial damage, we used a stereo-selective T-type calcium channel...

  • Atorvastatin modulates the DDAH1/ADMA system in high-fat diet-induced insulin-resistant rats with endothelial dysfunction. Chen, Po; Xia, Ke; Zhao, Zhenyu; Deng, Xu; Yang, Tianlun // Vascular Medicine;Dec2012, Vol. 17 Issue 6, p416 

    Dimethylarginine dimethyl-aminohydrolase 1 (DDAH1) is a metabolic enzyme for asymmetric dimethylarginine (ADMA), both of which are closely related to endothelial function. Endothelial dysfunction, a main risk factor of cardiovascular diseases, can be attributed to insulin resistance. We aimed to...

  • Does ADMA affect the oxidant/antioxidant balance in rats? ALAÇAM, Hasan; AVCI, Bahattin; ŞALIŞ, Osman; DİLEK, Ahmet; KOZAN, Ahmet; MERTOĞLU, Cuma; ŞAHİN, Mehmet; OKUYUCU, Ali // Turkish Journal of Medical Sciences;Jun2013, Vol. 43 Issue 3, p405 

    Aim: Asymmetric dimethylarginine (ADMA) is an inhibitor of nitric oxide synthase (NOS). Oxidative stress might be defined as an imbalance between protein oxidation and antioxidants. Our aim was to determine in vivo whether ADMA causes oxidative damage. Materials and methods: Thirty rats were...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics