title: The complex role of nitric oxide in the regulation of glomerular ultrafiltration.
abstract: The complex role of nitric oxide in the regulation of glomerular ultrafiltration. Nitric oxide is an important neurohumoral modulator of glomerular ultrafiltration and renal hemodynamics. Multiple nitric oxide synthase (NOS) isoforms are present within the kidney. However, it is difficult to discern which NOS is most active from prior studies using non-selective NOS blockers. It is recently apparent that NOS activity is important to the activity of tubuloglomerular feedback (TGF) systems, systems that relate tubular reabsorption to the regulation of glomerular ultrafiltration. Neuronal (nNOS) or brain NOS (bNOS; NOS I) is present within the macula densa, the sensing element of TGF systems. Inhibition of NOS activity and specifically bNOS enhances TGF activity. The TGF system also adapts temporally and these events appear to be dependent upon up-regulation of activity of bNOS within the kidney. Temporal adaptation occurs within one to three hours whereby activation of TGF is followed by a gradual return of the glomerular filtration rate (GFR) and renal blood flow toward normal levels. After 24 hours of benzolamide treatment and withdrawal of this agent, glomerular filtration actually increases to supranormal levels and this is prevented by inhibition of bNOS activity. Factors regulating bNOS activity have not been fully clarified. We have recently observed N-methyl-d-aspartate (NMDA) receptors within the kidney that, when inhibited, result in major reductions in renal blood flow and GFR, suggesting an important role for the NMDA receptor in regulation of renal hemodynamics. Future studies will determine whether NMDA receptor is also an important regulator of bNOS activity and the TGF system.
authors.affiliation: Division of Nephrology-Hypertension, Department of Medicine, University of California, San Diego, CA 92161, USA. rblantz@ucsd.edu
authors.forename: Roland C
authors.initials: RC
authors.lastname: Blantz
authors.forename: Aihua
authors.initials: A
authors.lastname: Deng
authors.forename: Mark
authors.initials: M
authors.lastname: Lortie
authors.forename: Karen
authors.initials: K
authors.lastname: Munger
authors.forename: Volker
authors.initials: V
authors.lastname: Vallon
authors.forename: Francis B
authors.initials: FB
authors.lastname: Gabbai
authors.forename: Scott C
authors.initials: SC
authors.lastname: Thomson
mesh_terms: D000818:Animals; D005919:Glomerular Filtration Rate; D007678:Kidney Glomerulus / Q000502:physiology*; D007684:Kidney Tubules / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase