Dimethylarginine dimethylaminohydrolase (DDAH)--a critical regulator of hypertensive left ventricular hypertrophy?
Left ventricular hypertrophy (LVH) is an early manifestation of cardiovascular target organ damage in patients with arterial hypertension. It is not only a target organ response to increased after-load, but is also the most potent cardiovascular risk factor. LVH is multifactorial sign which has several causative factors in addition to blood pressure. Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase. ADMA plasma levels have been shown to be elevated in diseases related to endothelial dysfunction such as hypertension, hyperlipidemia, diabetes mellitus. Because cardiac remodeling is associated with endothelial NO pathway, some recent studies investigated whether the plasma ADMA was related to LVH and found that there is a link between ADMA and left ventricular mass and geometry. ADMA was two times higher in patients with concentric LVH than in those normal controls. In many experimental systems, accumulation of ADMA is accompanied by reduced dimethylarginine dimethylaminohydrolase (DDAH) activity. Plasma ADMA is cleared in small part by urinary excretion, but the bulk of ADMA is degraded by DDAH. Therefore, we proposed that change in DDAH activity could disturb the metabolism of ADMA and result in hypertensive LVH through the ADMA/NO pathway.
Bai
Yongyi
Y
Hypertension Division, FuWai Hospital and Cardiovascular Institute, 167 Beilishilu, Beijing 100037, PR China.
Hui
Rutai
R
D000581:Amidohydrolases / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000737:chemistry; D002318:Cardiovascular Diseases / Q000473:pathology; D003920:Diabetes Mellitus / Q000473:pathology; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D006973:Hypertension; D017379:Hypertrophy, Left Ventricular / Q000473:pathology*; D051379:Mice; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D012306:Risk; D012307:Risk Factors
C487735:dimethylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000581:Amidohydrolases; C059999:dimethylargininase