Asymmetric dimethylarginine in angiotensin II-induced hypertension

Jennifer M. Sasser, Natasha C. Moningka, Mark W. Cunningham, Byron Croker, Chris Baylis

Research output: Contribution to journalArticlepeer-review

Abstract

Recent studies have shown that asymmetric dimethylarginine (ADMA), a nitric oxide synthase inhibitor, is increased in hypertension and chronic kidney disease. However, little is known about the effects of hypertension per se on ADMA metabolism. The purpose of this study was to test the hypothesis that ANG II-induced hypertension, in the absence of renal injury, is associated with increased oxidative stress and plasma and renal cortex ADMA levels in rats. Male Sprague-Dawley rats were treated with ANG II at 200 ng·kg -1·min-1 sc (by minipump) for 1 or 3 wk or at 400 ng·kg-1·min-1 for 6 wk. Mean arterial pressure was increased after 3 and 6 wk of ANG II; however, renal injury (proteinuria, glomerular sclerosis, and interstitial fibrosis) was only evident after 6 wk of treatment. Plasma thiobarbituric acid reactive substances concentration and renal cortex p22phox protein abundance were increased early (1 and 3 wk), but urinary excretion of isoprostane and H 2O2 was only increased after 6 wk of ANG II. An increased in plasma ADMA after 6 wk of ANG II was associated with increased lung protein arginine methyltransferase-1 abundance and decreased renal cortex dimethylarginine dimethylaminohydrolase activity. No changes in renal cortex ADMA were observed. ANG II hypertension in the absence of renal injury is not associated with increased ADMA; however, when the severity and duration of the treatment were increased, plasma ADMA increased. These data suggest that elevated blood pressure alone, for up to 3 wk, in the absence of renal injury does not play an important role in the regulation of ADMA. However, the presence of renal injury and sustained hypertension for 6 wk increases ADMA levels and contributes to nitric oxide deficiency and cardiovascular disease.

Original languageEnglish
Pages (from-to)R740-R746
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume298
Issue number3
DOIs
StatePublished - Mar 2010

Keywords

  • Dimethylarginine dimethylaminohydrolase
  • Kidney
  • Oxidative stress
  • Protein arginine methyltransferase-1

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