Neuronal nitric oxide synthase: its role and regulation in macula densa cells.

Academic Article


  • Macula densa (MD) cells detect changes in distal tubular sodium chloride concentration ([NaCl](L)), at least in part, through an apical Na:2Cl:K co-transporter. This co-transporter may be a site for regulation of tubuloglomerular feedback (TGF), and recently angiotensin II (Ang II) was shown to regulate the MD Na:2Cl:K co-transporter. In addition, nitric oxide (NO) produced via neuronal NO synthase (nNOS) in MD cells attenuates MD-TGF signaling. This study investigated [NaCl](L)-dependent MD-NO production, the regulation of co-transporter activity by NO, and the possible interaction of NO with Ang II. MD cell Na(+) concentration ([Na(+)](i)) and NO production were measured using sodium-binding benzofuran isophthalate and 4-amino-5-methylamino-2',7'-difluorescein diacetate, respectively, using fluorescence microscopy. Na:2Cl:K co-transport activity was assessed as the initial rate of increase in [Na(+)](i) when [NaCl](L) was elevated from 25 to 150 mM. 10(-4) M 7-nitroindazole, a specific nNOS blocker, significantly increased by twofold the initial rate of rise in [Na(+)](i) when [NaCl](L) was increased from 25 to 150 mM, indicating co-transporter stimulation. There was no evidence for an interaction between the stimulatory effect of Ang II and the inhibitory effect of NO on co-transport activity, and, furthermore, Ang II failed to alter MD-NO production. NO production was sensitive to [NaCl](L) but increased only when [NaCl](L) was elevated from 60 to 150 mM. These studies indicate that MD-NO directly inhibits Na:2Cl:K co-transport and that NO and Ang II independently alter co-transporter activity. In addition, generation of MD-NO seems to occur only at markedly elevated [NaCl](L), suggesting that NO may serve as a buffer against high rates of MD cell transport and excessive TGF-mediated vasoconstriction.
  • Authors


  • Angiotensin II, Animals, Arginine, Biological Transport, Enzyme Inhibitors, Indazoles, Juxtaglomerular Apparatus, Loop of Henle, Nitric Oxide, Nitric Oxide Donors, Nitric Oxide Synthase, Nitric Oxide Synthase Type I, Rabbits, Sodium Chloride, Sodium-Potassium-Chloride Symporters, Vasoconstrictor Agents
  • Pubmed Id

  • 23314326
  • Author List

  • Kovács G; Komlósi P; Fuson A; Peti-Peterdi J; Rosivall L; Bell PD
  • Start Page

  • 2475
  • End Page

  • 2483
  • Volume

  • 14
  • Issue

  • 10