title: L-arginine improves endothelial function, independently of arginine uptake, in aortas from chronic renal failure female rats.
abstract: Endothelial cell dysfunction (ECD) is a common feature of chronic renal failure (CRF). Defective nitric oxide (NO) generation due to decreased endothelial nitric oxide synthase (eNOS) activity is a crucial parameter characterizing ECD. Decreased activity of cationic amino acid transporter-1 (CAT-1), the selective arginine transporter of eNOS, has been shown to inhibit eNOS in uremia. Recently, we failed to demonstrate a decrease in glomerular arginine transport in uremic female rats (Schwartz IF, Grupper A, Soetendorp H, Hillel O, Laron I, Chernichovski T, Ingbir M, Shtabski A, Weinstein T, Chernin G, Shashar M, Hershkoviz R, Schwartz D. Am J Physiol Renal Physiol 303: F396-F404, 2012). The current experiments were designed to determine whether sexual dimorphism which characterizes glomerular arginine transport system in uremia involves the systemic vasculature as well and to assess the effect of L-arginine in such conditions. Contractile and vasodilatory responses, ultrastructural changes, and measures of the L-arginine-NO system were performed in thoracic aortas of female rats subjected to 5/6 nephrectomy. The contractile response to KCl was significantly reduced, and acetylcholine-induced vasodilation was significantly impaired in aortas from CRF dames compared with healthy rats. Both of these findings were prevented by the administration of arginine in the drinking water. The decrease in both cGMP generation, a measure of eNOS activity, and aortic eNOS and phosphorylated eNOS abundance observed in CRF rats was completely abolished by l-arginine, while arginine transport and CAT-1 protein were unchanged in all experimental groups. Arginine decreased both serum levels of advanced glycation end products and the asymmetrical dimethylarginine/arginine ratio and restored the endothelial ultrastructure in CRF rats. In conclusion. arginine administration has a profound beneficial effect on ECD, independently of cellular arginine uptake, in CRF female rats.
authors: Dept. of Nephrology, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, Israel 64239. idit.francesca@gmail.com.
authors: Nachum
authors: N
authors: Nesher
authors: Inna
authors: I
authors: Frolkis
authors: Doron
authors: D
authors: Schwartz
authors: Tamara
authors: T
authors: Chernichovski
authors: Sharon
authors: S
authors: Levi
authors: Yael
authors: Y
authors: Pri-Paz
authors: Gil
authors: G
authors: Chernin
authors: Alexander
authors: A
authors: Shtabsky
authors: Yanai
authors: Y
authors: Ben-Gal
authors: Yossi
authors: Y
authors: Paz
authors: Idit F
authors: IF
authors: Schwartz
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000503:physiopathology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats
chemical_list: D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP
keywords: arginine; chronic renal failure; endothelial dysfunction; nitric oxide