Consequences of acute nitric oxide synthesis inhibition in experimental glomerulonephritis

Romana Ferrario, Kihito Takahashi, Agnes Fogo, Kamal F. Badr, Karen A. Munger

Research output: Contribution to journalArticlepeer-review

Abstract

To assess the functional relevance of the enhanced glomerular nitric oxide (NO) synthesis during acute nephrotoxic serum (NTS) nephritis, a NO synthesis inhibitor (NOI) NG-monomethyl-L-arginine was administered to normal (N + NOI) and acutely nephritic (NTS + NOI) Munich-Wistar rats, and systemic and glomerular hemodynamic responses were contrasted with those observed in vehicle-treated normal and nephritic (NTS) controls. Urinary protein excretion rates were equal in normal and N + NOI rats but were markedly elevated in NTS animals and further increased in NTS+NOI. NO inhibition in normal animals (normal versus N + NOI) led to reductions in glomerular plasma flow rate and the glomerular capillary ultrafiltration coefficient (Kf) and elevations in afferent and efferent arteriolar resistances and net transcapillary hydraulic pressure difference (ΔP), as well as an increase in systemic arterial pressure. The increase in ΔP offset the falls in glomerular plasma flow rate and Kf, and GFR was preserved. Directionally similar responses in efferent resistance occurred in NTS + NOI compared with NTS, however, afferent resistance was not further affected by NOI. Additionally, although K, was severely depressed in the NTS group (∼60% versus normal), it was not further depressed by NOI treatment. Polymorphonuclear cell (PMN) infiltration/glomerulus was mildly increased in N + NOI over normal. In contrast, PMN number in NTS + NOI rats was diminished as compared with NTS. Thus, NO inhibition during inflammatory glomerular injury leads to a dramatic increase in proteinuria, likely as the result of marked exacerbation of the already elevated values of ΔP. Moreover, tonic release of NO plays a crucial role in the maintenance of baseline vascular resistance and Kf in normal glomeruli, but to a lesser extent in acutely inflamed glomeruli. The apparent amelioration of PMN infiltration in NTS + NOI rats remains unexplained but may be related to the severe fall in nephron perfusion.

Original languageEnglish (US)
Pages (from-to)1847-1854
Number of pages8
JournalJournal of the American Society of Nephrology
Volume4
Issue number11
StatePublished - May 1994
Externally publishedYes

Keywords

  • GFR
  • Mesangial cell
  • N-monomethyl-L-arginine
  • Proteinuria
  • RBF

ASJC Scopus subject areas

  • Nephrology

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