Oxygen modulation of guanylate cyclase-mediated retinal pericyte relaxations with 3-morpholino-sydnonimine and atrial natriuretic peptide.
OBJECTIVE
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-1) or atrial natriuretic peptide (ANP) in the absence or in the presence of either 0.3 microM methylene blue (MB), a guanylate cyclase inhibitor, or 10 microM hemoglobin, a NO scavenger; and under 100% oxygen (hyperoxia), ambient air (normoxia), or 100% nitrogen (hypoxia).


RESULTS
Pericytes were relaxed with SIN-1 and ANP in a concentration-dependent manner (EC50: 0.1 microM and 0.01 microM, respectively). Relaxations induced by SIN-1 or ANP were inhibited (P < 0.001) by MB, whereas hemoglobin inhibited only SIN-1 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-1 and ANP relax pericytes through the activation of guanylate cyclase (inhibited by MB), but only SIN-1 through an extracellular release of NO (inhibited by hemoglobin). That oxygen only modulates pericyte relaxations induced by SIN-1 (NO-mediated) but not those induced by ANP suggests that an interaction between oxygen and NO might participate in the capillary network's blood-flow modulation according to local tissue oxygen tension.
Haefliger
I O
IO
Department of Opthalmology, Bascom Palmer Eye Institute, University Miami School of Medicine, Florida, USA.
Anderson
D R
DR
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D006162:Guanylate Cyclase / Q000502:physiology*; D006454:Hemoglobins / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D010100:Oxygen / Q000494:pharmacology*; D012171:Retinal Vessels / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D006454:Hemoglobins; D014665:Vasodilator Agents; D009569:Nitric Oxide; C002385:linsidomine; D009320:Atrial Natriuretic Factor; D008981:Molsidomine; D006162:Guanylate Cyclase; D010100:Oxygen; D008751:Methylene Blue