Effects of endothelium-derived relaxing factor and nitric oxide on rat mesangial cells

P. J. Shultz, A. E. Schorer, L. Raij

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126 Scopus citations

Abstract

We have investigated whether endothelium-derived relaxing factor (EDRF) and nitric oxide (NO), a substance proposed to be one of the EDRFs, could elicit biochemical and biological responses in rat glomerular mesangial cells (MC). In wells with MC alone, guanosine 3′,5′-cyclic monophosphate (cGMP) levels were 2.6 ± 0.6 fmol/ μg protein, and bradykinin did not affect these levels, whereas in coincubation experiments with bovine aortic EC and rat MC, cGMP, levels in MC increased to 44.6 ± 21 fmol/μg protein after bradykinin stimulation (P < 0.05). This effect was potentiated by superoxide dismutase and inhibited by hemoglobin and L-NG-monomethyl arginine, a specific inhibitor of EDRF synthesis. Increases in cGMP were also observed when MC were incubated directly with NO and were potentiated by superoxide dismutase and inhibited by hemoglobin. We also tested whether NO could inhibit angiotensin II (ANG II)induced reductions in cross-sectional area (CSA) of MC. When MC were exposed to ANG II only, 65% of the cells underwent a significant reduction in CSA, as measured by digital image analysis. However, when MC were incubated with ANG II and NO, only 10% of cells responded (P < 0.04). These studies demonstrate that EDRF and NO induce significant biochemical and functional responses in rat glomerular MC and suggest that communication between EC and MC may be important in regulation of glomerular function.

Original languageEnglish (US)
Pages (from-to)F162-F167
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume258
Issue number1 27-1
DOIs
StatePublished - 1990

Keywords

  • 5′cyclic monophosphate
  • Angiotensin ii
  • Endothelial cells
  • Guanosine 3′
  • L-n-monomethyl arginine
  • Mesangial cell cross-sectional area

ASJC Scopus subject areas

  • Physiology

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