Macula densa nitric oxide synthase: expression, regulation, and function.
The type 1 brain nitric oxide synthase (bNOS) isoform occurs in macula densa (MD) cells where it functions to vasodilate the afferent arteriole and blunt expression of tubuloglomerular feedback (TGF). Dietary salt restriction enhances bNOS expression, yet microperfusion studies with NOS inhibitors imply that it is functionally inactive. We thus assessed the hypothesis that reduced L-arginine (L-Arg) availability during low salt (LS) intake limits MD NO generation. Maximal TGF responses were recorded during Henle's loop perfusion with artificial tubular fluid (ATF). Microperfusion of L-Arg into the MD of LS, but not normal or high-salt (HS) rats blunted maximal TGF responses (8.0 +/- 0.4 to 6.0 +/- 0.5 mm Hg; N = 23; P < 0.01). Response to L-Arg was stereospecific, inhibited by coperfusion with monomethyL-L-arginine (L-NMA), and dependent on system y+ transport, because it was blocked by coperfusion with the competitors L-lysine or L-homoarginine. Absorption of [3H]-L-Arg from the perfused loop, via an L-Arg- or L-homoarginine-inhibitable process, was enhanced during HS. Salt restriction thus diminishes TGF attenuation by NO in the MD despite enhanced bNOS expression because of limited delivery and/or uptake of L-Arg via system y+. This defines a novel mechanism of renal microcirculatory adaptation to salt restriction via L-Arg-dependent changes in TGF.
Wilcox
C S
CS
Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, DC 20007, USA. wilcoxch@gunet.georgetown.edu
Welch
W J
WJ
D000818:Animals; D001120:Arginine / Q000493:pharmacokinetics; D001667:Binding, Competitive / Q000502:physiology; D001692:Biological Transport / Q000502:physiology; D001794:Blood Pressure; D002352:Carrier Proteins / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D007606:Juxtaglomerular Apparatus / Q000098:blood supply / Q000737:chemistry / Q000201:enzymology*; D008239:Lysine / Q000493:pharmacokinetics; D008297:Male; D008833:Microcirculation / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D009952:Ornithine / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000502:physiology
D002352:Carrier Proteins; D001120:Arginine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D008239:Lysine