Effects of acute and chronic L-arginine treatment in experimental hyperuricemia.
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.
Sánchez-Lozada
Laura G
LG
Dept. of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1. 14080, Mexico City, Mexico. lgsanchezlozada@hotmail.com
Tapia
Edilia
E
López-Molina
Rubén
R
Nepomuceno
Tomás
T
Soto
Virgilia
V
Avila-Casado
Carmen
C
Nakagawa
Takahiko
T
Johnson
Richard J
RJ
Herrera-Acosta
Jaime
J
Franco
Martha
M
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D033461:Hyperuricemia / Q000150:complications* / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009566:Nitrates / Q000652:urine; D009573:Nitrites / Q000652:urine; D010094:Oxonic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley
D009566:Nitrates; D009573:Nitrites; D010094:Oxonic Acid; D001120:Arginine