Effect of arginine depletion on glomerular and tubular kidney function: studies in isolated perfused rat kidneys.
The effect of L-Arg depletion on glomerular hemodynamics and tubular function of isolated rat kidneys perfused with a medium containing 21 amino acids has been studied. A cyclooxygenase inhibitor was added throughout for blockade of prostaglandin synthesis. Arg depletion caused significant (approximately 30%) reductions in renal perfusion flow rate (PFR, 13.9 +/- 1.2 vs. 19.8 +/- 0.6 ml.min-1.g (kidney wt-1), glomerular filtration rate (GFR, 598 +/- 79 vs. 924 +/- 42 microliters.min-1.g kidney wt-1), and urine flow rate (139 +/- 38 vs. 192 +/- 13 microliters.min-1.g kidney wt-1) compared with control kidneys, which were perfused with a physiological concentration of Arg (200 microM). Filtration fraction (FF) increased with Arg depletion (5.1 +/- 0.4 vs. 4.4 +/- 0.4%). Arg-depleted kidneys had a lower absolute sodium (TNa, 75.7 +/- 8.8 vs. 107.9 +/- 6.0 mumol.min-1.g kidney wt-1) and glucose reabsorption (T glucose, 3.7 +/- 0.6 vs. 5.6 +/- 0.5 mumol.min-1.g kidney wt-1), corresponding to a lower sodium and glucose filtration. Potassium handling and reabsorption of free water were not changed. Oxygen consumption (QO2) was lower in Arg-depleted kidneys (4.6 +/- 0.3 vs. 5.5 +/- 0.5 mumol.min-1.g kidney wt-1). The effects of Arg depletion were completely reversed by the addition of Arg (1 mM) at 120 min and partly reversed by the addition of citrulline (1 mM). Ornithine depletion or addition had no effect on PFR, GFR, FF, TNa, T glucose, and QO2. N omega-methyl-L-arginine, a specific inhibitor of nitric oxide endothelium-derived relaxing factor, produced the same effect as Arg depletion.(ABSTRACT TRUNCATED AT 250 WORDS)
Radermacher
J
J
Department of Clinical Pharmacology, Hannover Medical School, Federal Republic of Germany.
Klanke
B
B
Kastner
S
S
Haake
G
G
Schurek
H J
HJ
Stolte
H F
HF
Frölich
J C
JC
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000172:deficiency / Q000494:pharmacology*; D001834:Body Water / Q000378:metabolism; D002956:Citrulline / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000502:physiology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000502:physiology*; D007684:Kidney Tubules / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009952:Ornithine / Q000494:pharmacology; D010477:Perfusion / Q000379:methods; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013997:Time Factors; D014556:Urine / Q000502:physiology; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D002956:Citrulline; D001120:Arginine; D012964:Sodium; D009952:Ornithine; D005947:Glucose