Feedback control of glomerular vascular tone in neuronal nitric oxide synthase knockout mice.
For further elucidation of the role of neuronal nitric oxide synthase (nNOS) in macula densa (MD) cells, experiments were performed in anesthetized nNOS knockout mice (nNOS -/-). At comparable levels of arterial BP, renal blood flow was not significantly different between nNOS +/+ and nNOS -/- (1.7 +/- 0.2 versus 1.4 +/- 0.1 ml/min), and autoregulation of renal blood flow was maintained to a pressure level of approximately 85 mmHg in both groups of mice (n = 6 in each group). The fall in proximal tubular stop-flow pressure in response to an increase in loop of Henle perfusion rate from 0 to 30 nl/min was comparable in nNOS +/+ and -/- mice (40.7 +/- 1.6 to 32 +/- 2 mmHg versus 40.6 +/- 1.6 to 31.6 +/- 2 mmHg; not significant; n = 13 versus 18 nephrons). Luminal application of the nonselective NOS inhibitor nitro-L-arginine (10(-3) and 10(-2) M) enhanced the perfusion-dependent fall in stop-flow pressure in nNOS +/+ (7 +/- 1 to 13 +/- 2 mmHg; P < 0.05) but not in nNOS -/- (7 +/- 1 to 8 +/- 1 mmHg; not significant) mice. nNOS -/- mice exhibited a lower nephron filtration rate, compared with nNOS +/+, during free-flow collections from early distal tubules (influence of MD intact, 7 +/- 0.7 versus 10.9 +/- 1 nl/min; P = 0.002) but not from late proximal tubule (influence of MD minimized, 10.1 +/- 1 versus 11.7 +/- 1 nl/min; not significant; n = 16 nephrons). Distal Cl concentration and fractional absorption of fluid or chloride up to the early distal tubule was not different between nNOS -/- and +/+ mice. The data indicate that nNOS in MD tonically attenuates the GFR-lowering influence of ambient luminal NaCl, which may serve to increase the fluid and electrolyte load to the distal tubule, consistent with a role of MD nNOS in tubuloglomerular feedback resetting.
Vallon
Volker
V
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Traynor
Timothy
T
Department of Medicine, University of Michigan, Ann Arbor, Michigan.
Barajas
Luciano
L
Department of Pathology, UCLA-Harbor Medical Center, Torrance, California.
Huang
Yuning G
YG
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Briggs
Josie P
JP
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Schnermann
Jürgen
J
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005246:Feedback; D005260:Female; D006706:Homeostasis; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000098:blood supply*; D007684:Kidney Tubules / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D019335:Nitroarginine / Q000494:pharmacology; D011677:Punctures; D012016:Reference Values; D012079:Renal Circulation / Q000502:physiology*; D014666:Vasomotor System / Q000502:physiology*
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse