Cyclic GMP Mediates Influence of Macula densa Nitric Oxide over Tubuloglomerular Feedback

Abstract

Background: Tubuloglomerular feedback (TGF) stabilizes nephron function by eliciting reciprocal changes in single-nephron glomerular filtration rate in response to changes in salt reaching the macula densa. Nitric oxide (NO) modulates TGF, making it less reactive. NO could come from NO synthase (NOS) in mesangium or microvessels (NOS III) or from neuronal NOS (NOS I) in the macula densa. Cyclic GMP is second messenger for many NO functions. Methods: Rat micropuncture was performed to confirm that macula densa NOS I makes the NO which modulates TGF and that cyclic GMP is a second messenger for this. The range of TGF was determined by measuring the single-nephron glomerular filtration rate while perfusing Henle’s loop. The TGF slope was calculated from the response to flow perturbations in free-flowing nephrons using a noninvasive optical technique to measure flow. The NO-cyclic GMP axis was manipulated by tubular microperfusion of the antagonists S-methyl-thiocitrulline (SMTC) and 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) and NO donor (spermine NONOate). Results: SMTC and ODQ each increased slope and range of TGF and tended to shift it leftward. NONOate reversed the effects of SMTC, but not of ODQ. Conclusion: Cyclic GMP mediates desensitization of TGF by macula densa NOS I.

Journal

Journal ID (publisher-id): KBR

Journal ID (nlm-ta): Kidney Blood Press Res

Journal ID (doi): 10.1159/issn.1420-4096

Title: Kidney and Blood Pressure Research

Publisher: S. Karger AG

ISSN (Print): 1420-4096

ISSN (Electronic): 1423-0143

Publication date Subscription-year: 2003

Publication date (Print): 2003

Publication date (Electronic): 24 April 2003

Volume: 26

Issue: 1

Pages: 10-18

Affiliations

Department of Medicine, Veterans Affairs Medical Center and University of California, San Diego, Calif., USA

Article

Publisher ID: 69766 Other ID: Kidney Blood Press Res 2003;26:10–18

DOI: 10.1159/000069766

PubMed ID: 12697972

Copyright statement: © 2003 S. Karger AG, Basel

License:

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Page count

Figures: 4, References: 26, Pages: 9

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Categories

Subject: Original Paper