Putative role of asymmetric dimethylarginine in microvascular disease of kidney and heart in hypertensive patients

BACKGROUND Despite the frequent simultaneous presentation of cardiac and renal dysfunction, the relationship between these pathophysiological processes remains unclear. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase, which has been linked to endothelial dysfunction and atherosclerosis. This study elucidates the relationship between ADMA and intrarenal and coronary microvascular diseases. METHODS In this study, we included 66 consecutive hypertensive patients with normal renal function or mild renal insufficiency (creatinine <= 1.2 mg/dl). On the basis of their estimated glomerular filtration rate (eGFR), the patients were divided into two groups (normal group, eGFR >= 90 ml/min; renal insufficiency group, eGFR <90 ml/min). Coronary flow velocity reserve (CFVR) was measured using adenosine-triphosphate stress transthoracic Doppler echocardiography. In addition, a plasma ADMA assay, echocardiography, carotid ultrasound, and brachial-ankle pulse wave velocity measurement were performed. RESULTS The plasma ADMA level was the highest in patients with both renal insufficiency and reduced CFVR. ADMA was significantly associated with eGFR (r= -0.342, P = 0.006) and CFVR (r = -0.459, P < 0.001), and eGFR and CFVR were significantly associated with each other (r= 0.337, P = 0.006). Multiple regression analysis revealed that ADMA was an independent clinical parameter associated with both eGFR and CFVR. CONCLUSIONS Plasma ADMA is suggested to be an incipient biochemical marker of microvascular disease in both kidney and heart in hypertensive patients. ADMA might play an important role in the pathogenesis of organ damage in the kidney and heart in essential hypertension.