Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Welch, W.J. et al.

Macula densa arginine delivery and uptake in the rat regulates glomerular capillary pressure. Effects of salt intake.

These studies tested the hypothesis that delivery and/or cellular uptake of L-arginine limits macula densa nitric oxide generation and actions on tubuloglomerular feedback (TGF) during salt restriction. Maximal TGF responses were assessed from reductions in proximal stop flow pressure during loop of Henle (LH) perfusion at 40 nl/min with artificial tubular fluid containing vehicles or drugs. Orthograde LH perfusion of L-arginine (10[-3] M) reduced maximal TGF significantly in rats adapted to low salt (LS: 7.9+/-0.4-6.3+/-0.4 mmHg; P < 0.05), but not high salt (HS: 5.8+/-0.3-5.9+/-0.3; NS). The effects were stereospecific and prevented by coperfusion with NG-methyl-L-arginine. Microperfusion of L-arginine (10[-3] M) into the peritubular capillaries reduced the maximum TGF response more in nephrons of LS than HS rats (deltaTGF: LS, 32+/-6 vs. HS, 13+/-4%; P < 0.05) and restored a TGF response to luminal perfusion of NG-methyl-L-arginine in LS rats. Coperfusion of nephrons with excess L-lysine or L-homoarginine, which compete with L-arginine for system y+ transport, blocked the fall in proximal stopflow pressure produced by orthograde LH perfusion of L-arginine in LS rats. Reabsorption of [3H]arginine by the perfused loop segment was similar in LS (93+/-2%) and HS (94+/-1%) rats. Coperfusion with excess L-arginine, L-lysine, or L-homoarginine, however, reduced [3H]arginine reabsorption significantly (P < 0.05) more in HS rats than in LS rats. In conclusion, blunting of maximal TGF responses in salt-restricted rats by nephron-derived NO is limited by L-arginine availability and cellular uptake via system y+.[1]

References

Macula densa arginine delivery and uptake in the rat regulates glomerular capillary pressure. Effects of salt intake. Welch, W.J., Wilcox, C.S. J. Clin. Invest. (1997) [Pubmed]

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