Dimethylarginine dimethylaminohydrolase (DDAH): Expression, regulation and function in the cardiovascular and renal systems
2007 (English)In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 293, no 6, H3227-H3245 p.Article in journal (Refereed) Published
Asymmetric (NG,NG)-dimethylarginine (ADMA) inhibits nitric oxide(NO) synthases (NOS). ADMA is a risk factor for endothelialdysfunction, cardiovascular mortality, and progression of chronickidney disease. Two isoforms of dimethylarginine dimethylaminohydrolase(DDAH) metabolize ADMA. DDAH-1 is the predominant isoform inthe proximal tubules of the kidney and in the liver. These organsextract ADMA from the circulation. DDAH-2 is the predominantisoform in the vasculature, where it is found in endothelialcells adjacent to the cell membrane and in intracellular vesiclesand in vascular smooth muscle cells among the myofibrils andthe nuclear envelope. In vivo gene silencing of DDAH-1 in therat and DDAH +/– mice both have increased circulatingADMA, whereas gene silencing of DDAH-2 reduces vascular NO generationand endothelium-derived relaxation factor responses. DDAH-2also is expressed in the kidney in the macula densa and distalnephron. Angiotensin type 1 receptor activation in kidneys reducesthe expression of DDAH-1 but increases the expression of DDAH-2.This rapidly evolving evidence of isoform-specific distributionand regulation of DDAH expression in the kidney and blood vesselsprovides potential mechanisms for nephron site-specific regulationof NO production. In this review, the recent advances in theregulation and function of DDAH enzymes, their roles in theregulation of NO generation, and their possible contributionto endothelial dysfunction in patients with cardiovascular andkidney diseases are discussed.
Place, publisher, year, edition, pages
2007. Vol. 293, no 6, H3227-H3245 p.
nitric oxide synthase, hypertension, diabetes mellitus, chronic kidney disease, asymmetric dimethylarginine
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-99295DOI: 10.1152/ajpheart.00998.2007PubMedID: 17933965OAI: oai:DiVA.org:liu-99295DiVA: diva2:657238