Oxygen modulation of guanylate cyclase-mediated retinal pericyte relaxations with 3-morpholino-sydnonimine and atrial natriuretic peptide

Ivan O. Haefligef, Douglas R. Anderson

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Purpose: This study explores at which level of the guanylate cyclase pathway oxygen modulates retinal pericyte relaxation induced by nitric oxide (NO). Methods: Bovine retinal microvascular pericytes were grown on silicone. On silicone, pericyte contractile tone induces wrinkles. Drug-induced relaxation was quantified as a reduced number of wrinkles after exposure to 3-morpholino-sydnonimine (SIN-I) or atrial natriuretic peptide (ANP) in the absence or in the presence of either 0.3 μM methylene blue (MB), a guanylate cyclase inhibitor, or 10 μM hemoglobin, a NO scavenger; and under 100% oxygen (hyperoxia), ambient air (normoxia), or 100% nitrogen (hypoxia). Results: Pericytes were relaxed with SIN-I and ANP in a concentration- dependent manner (EC 50:0.1 μM and 0.01 μM, respectively). Relaxations induced by SIN-I or ANP were inhibited (P < 0.001) by MB, whereas hemoglobin inhibited only SIN-I relaxations (P < 0.001). Relaxations induced by SIN-1, but not by ANP were increased (P < 0.001) under hypoxia and decreased (P=0.002) under hyperoxia. Conclusions: SIN-I and ANP relax pericytes through the activation of guanylate cyclase (inhibited by MB), but only SIN-I through an extracellular release of NO (inhibited by hemoglobin). That oxygen only modulates pericyte relaxations induced by SIN-I (NO-mediated) but not those induced by ANP suggests that an interaction between oxygen anti NO might participate in the capillary network's blood-flow modulation according to local tissue oxygen tension.

Original languageEnglish (US)
Pages (from-to)1563-1568
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume38
Issue number8
StatePublished - Aug 12 1997

Keywords

  • Eye
  • Free radicals
  • Glaucoma
  • Optic nerve head circulation
  • Retina

ASJC Scopus subject areas

  • Ophthalmology

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