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

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          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.

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          Most cited references 3

          • Record: found
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          Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle.

          Nitric oxide is the major endothelium-derived relaxing factor (EDRF), and it is thought to relax smooth muscle cells by stimulation of guanylate cyclase, accumulation of its product cyclic GMP, and cGMP-dependent modification of several intracellular processes, including activation of potassium channels through cGMP-dependent protein kinase. Here we present evidence that both exogenous nitric oxide and native EDRF can directly activate single Ca(2+)-dependent K+ channels (K+Ca) in cell-free membrane patches without requiring cGMP. Under conditions when guanylate cyclase was inhibited by methylene blue, considerable relaxation of rabbit aorta to nitric oxide persisted which was blocked by charybdotoxin, a specific inhibitor of K+Ca channels. These studies demonstrate a novel direct action of nitric oxide on K+Ca channels.
            • Record: found
            • Abstract: not found
            • Article: not found

            Accelerated reaction of nitric oxide with O2 within the hydrophobic interior of biological membranes

             X. Liu,  M. Miller,  M S Joshi (1998)
              • Record: found
              • Abstract: not found
              • Article: not found

              Inhibition of Ecto-5`-nucleotidase by Nitric Oxide Donors


                Author and article information

                Kidney Blood Press Res
                Kidney and Blood Pressure Research
                S. Karger AG
                24 April 2003
                : 26
                : 1
                : 10-18
                Department of Medicine, Veterans Affairs Medical Center and University of California, San Diego, Calif., USA
                69766 Kidney Blood Press Res 2003;26:10–18
                © 2003 S. Karger AG, Basel

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                Figures: 4, References: 26, Pages: 9
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