Feedback Control of Glomerular Vascular Tone in Neuronal... : Journal of the American Society of Nephrology (original) (raw)

Cell and Transport Physiology

Feedback Control of Glomerular Vascular Tone in Neuronal Nitric Oxide Synthase Knockout Mice

VALLON, VOLKER*; TRAYNOR, TIMOTHY†; BARAJAS, LUCIANO‡; HUANG, YUNING G.*; BRIGGS, JOSIE P.*; SCHNERMANN, JU[Combining Diaeresis]RGEN*

*National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

†Department of Medicine, University of Michigan, Ann Arbor, Michigan

‡Department of Pathology, UCLA-Harbor Medical Center, Torrance, California.

Correspondence to Dr. Jurgen Schnermann, NIDDK, NIH, Building 10, Room 4 D51, 10 Center Drive MSC 1370, Bethesda, MD. Phone: 301-435-6580; Fax: 301-435-6587; E-mail: [email protected]

Accepted February 1, 2001

Received December 7, 2000

Abstract

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.