Nitric oxide synthase derangements and hypertension in kidney disease

作者：Baylis Chris^*

来源：Current Opinion in Nephrology and Hypertension, 2012, 21(1): 1-6.

DOI：10.1097/MNH.0b013e32834d54ca

• asymmetric dimethylarginine
• dimethylarginine dimethylaminohydrolase
• nitric oxide synthase

Purpose of review
Nitric oxide deficiency occurs by multiple mechanisms and contributes to the pathogenesis of progression of chronic kidney disease (CKD) and its cardiovascular complications. This article concentrates on recent developments on the regulation of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in CKD and on the importance of the nitric oxide synthases in kidney disease progression, particularly in diabetic nephropathy.
Recent findings
The increased plasma ADMA seen in renal disease is generally predictive of severity of CKD progression and cardiovascular risk. However, some assumptions about the control of ADMA have been challenged: the primacy of the kidney as a metabolic organ for plasma ADMA regulation has come under scrutiny and the relative importance of the two isoforms of the ADMA-metabolizing enzymes dimethylarginine dimethylaminohydrolases (DDAHs) is being re-evaluated. Alterations in NOS also contribute to CKD progression with the endothelial isoform playing a major role in diabetic nephropathy.
Summary
Improving our understanding of ADMA regulation is important since pharmacologic targeting of DDAH is underway. The major role of endothelial NOS-derived nitric oxide in diabetic nephropathy should lead to novel therapies. The beneficial actions of dietary nitrate supplementation on blood pressure and kidney disease are of considerable clinical relevance.

• 出版日期2012-1