Effects of acute and chronicl-arginine treatment in experimental hyperuricemia

Abstract

Experimental hyperuricemia (HU) results in preglomerular arteriolopathy, cortical vasoconstriction, and glomerular hypertension. Recently, uric acid has been shown to induce endothelial dysfunction. We therefore studied the effect of acute and chronic administration of l-arginine (a substrate for endothelial nitric oxide synthase) on the renal hemodynamic and vascular structural alterations induced by HU. To induce HU, oxonic acid (OA; 750 mg.kg(-1).day(-1)) was administered in male Sprague-Dawley rats. To study the acute effect of arginine, nine rats received l-arginine (l-Arg; 15 mg.kg(-1).min(-1)) during micropuncture. To elucidate the chronic effect of l-Arg, OA + 1% l-Arg (n = 8) and OA + 2.5% l-Arg (n = 6; drinking water) were evaluated throughout the 5-wk period. Eight normal control (N), and eight OA, rats were also studied. Kidneys were fixed by perfusion and afferent arteriole morphology was evaluated. HU rats developed the renal functional and structural alterations described and had suppressed urinary excretion of NO(2)(-)/NO(3)(-). Acute stimulation of nitric oxide (NO) synthesis markedly increased urinary NO(2)(-)/NO(3)(-), lowered systemic blood pressure, and relieved cortical vasoconstriction despite a significant increment of glomerular hypertension and afferent arteriole damage. Increasing doses of chronic l-Arg were associated with increasing excretion of urinary NO(2)(-)/NO(3)(-), reduction of systemic hypertension, and prevention of cortical vasoconstriction (2.5% l-Arg). In addition, both doses prevented glomerular hypertension and preglomerular arteriolopathy. Thus an acute relief of renal vasoconstriction in the setting of afferent arteriole damage cannot reverse glomerular hypertension, likely due to impairment in preglomerular autoregulation. On the other hand, chronic l-Arg preserved arteriolar structures probably mediated by the antiproliferative effect of NO on vascular smooth muscle cells.

Prognostic Significance of Hyperuricemia in Patients with Different Types of Renal Dysfunction and Acute Myocardial Infarction Treated with Percutaneous Coronary Intervention

“…Experimental studies indicate direct and unfavorable effects of uric acid on vascular and renal biology [35,36,37,38,39]. Studies show that elevated uric acid concentrations cause endothelial dysfunction leading to the reduction in endothelial levels of nitric oxide and, thus, to renal vasoconstriction [40,41]. The influence of high uric acid concentration on vascular smooth-muscle cells is expressed through the intensification of cellular proliferation, inflammation and activation of the local renin-angiotensin system [35,37].…”

Relationship of Serum Asymmetric Dimethylarginine Levels with Inflammation and Cardiac Functions in Autosomal Dominant Polycystic Kidney Disease

“…In various studies, SUA levels have been thought to be an important marker for ED and an early indicator of vascular injury in renal failure, HT and CVD (41,42). In a study using endothelial cell cultures, SUA decreased NO synthesis (43) and was shown to contribute to ED by gaining a pro-oxidative property (44,45). In ADPKD, the SUA levels increased as a result of a decrease in GFR (46)(47)(48) and high SUA levels were related to early onset HT and renal disease progression (49).…”

Redox Control of Renal Function and Hypertension

“…Experimentally increased uric acid levels result in accelerated renal-disease progression by variably increasing systolic BP, afferent glomerular arteriolopathy, oxidative stress, and endothelial dysfunction in different rat models, and administration of allopurinol reversed these deleterious effects (149,158). In addition, reduction of BP with enalapril and potentiation of NO with NOS substrate L-arginine also variably improved renal function (209,283). However, the role of uric acid as a risk factor for kidney disease is largely unknown (145).…”