• Background: This study addresses whether oxygen modulates the relaxation induced in retinal pericytes by sodium nitroprusside (SNP), a nitric oxide (NO) donor that stimulates the NO/guanylate cyclase pathway. • Methods:Bovine retinal pericytes were cultured on silicone. On the silicone surface, basal pericyte contractile tone induces wrinkles. Drug-induced changes in pericyte contractile tone were assessed by changes in the number of wrinkles. The effects of 100% nitrogen (hypoxia) and 100% oxygen (hyperoxia) were studied on: (a) the basal tone of quiescent pericytes, (b) the relaxation to 3 and 10 μM SNP or 1 μM forskolin, and (c) the recontraction that followed the washout of 3 μM SNP or 1 μM forskolin. • Results: Neither hypoxia nor hyperoxia had any apparent influence on pericyte basal tone, on forskolin-induced relaxation, or on pericyte recontraction after a forskolin-induced relaxation. In hypoxia, relaxations to SNP 3 μM (P<0.05) and 10 μM (P<0.01) were significantly more pronounced than in hyperoxia. Hypoxia also reduced the recontraction after an SNP-induced relaxation (P<0.001). • Conclusion: Oxygen modulates the relaxation of bovine retinal pericytes evoked by SNP (guanylate cyclase-mediated), but not the relaxation induced by forskolin (adenylate cyclase-mediated). These results suggest that in the retinal capillary circulation an interaction between oxygen and the NO/guanylate cyclase pathway modulates pericyte tone, and thus potentially blood flo
