Prostanoid production in rabbit corpus cavernosum .2. Inhibition by oxidative stress

Purpose: To investigate the effects of reoxygenation following hypoxia on prostanoid production in rabbit penile corpus cavernosum tissue (RCC) in organ culture. Materials and Methods: Strips of RCC were incubated in organ culture media under either 21% O-2 (control, PO2 similar to 167 mm.Hg) or 0% O-2 (hypoxia, PO2 similar to 27 mm.Hg) followed by a reoxygenation period with 21% O-2, in the presence or absence of exogenous arachidonate, Tiron or catalase. Prostanoids were measured in collected media by radioimmunoassay. Malondialdehyde levels were measured in RCC following exposure to either control or hypoxia-reoxygenation conditions. Results: Under hypoxic conditions, basal release of prostanoids (PGI(2), PGF2(alpha), PGE(2) and TXB(2)) was inhibited. Although this inhibition was reversible upon reoxygenation, the recovery was delayed, requiring at least 2 hours of exposure to 21% oxygen to reestablish prostanoid production. Reoxygenation also caused lipid peroxidation as measured by an increase in malondialdehyde levels. When reoxygenation was done in the presence of exogenous arachidonate, recovery of PGI(2) production was complete by 1 hour. Reoxygenation in the presence of a scavenger of reactive oxygen species (Tiron) or catalase significantly improved the recovery rate of PGI(2) production. Conclusions: These results show that reoxygenation of hypoxic tissue generates oxidative stress that interferes with the recovery of prostanoid production by alteration of a biosynthetic point(s) upstream from prostaglandin H synthase (PGHS) including, at least, phospholipid peroxidation.