OXYGEN MODULATION OF GUANYLATE CYCLASE-MEDIATED RETINAL PERICYTE RELAXATIONS WITH 3-MORPHOLINO-SYDNONIMINE AND ATRIAL-NATRIURETIC-PEPTIDE

Purpose. This study explores at which level of the guanylate cyclase p athway 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 wrinkle s after exposure to 3-morpholino-sydnonimine (SIN-1) or atrial natriur etic peptide (ANP) in the absence or in the presence of either 0.3 mu M methylene blue (MB), a guanylate cyclase inhibitor, or 10 mu M hemog lobin, a NO scavenger; and under 100% oxygen (hyperoxia), ambient air (normoxia), or 100% nitrogen (hypoxia). Results. Pericytes were relaxe d with SIN-1 and ANP in a concentration-dependent manner (EC50: 0.1 mu M and 0.01 mu M, respectively). Relaxations induced by SIN-1 or ANP w ere inhibited (P < 0.001) by MB, whereas hemoglobin inhibited only SIN -1 relaxations (P < 0.001). Relaxations induced by SIN-1, but not by A NP were increased (P < 0.001) under hypoxia and decreased (P = 0.002) under hyperoxia. Conclusions. SIN-1 and ANP relax pericytes through th e activation of guanylate cyclase (inhibited by MB), but only SIN-1 th rough an extracellular release of NO (inhibited by hemoglobin). That o xygen only modulates pericyte relaxations induced by SIN-1 (NO-mediate d) but not those induced by ANP suggests that an interaction between o xygen and NO might participate in the capillary network's blood-flow m odulation according to local tissue oxygen tension.