ABSTRACT
Noise exposure induces the formation in the cochlea of 8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)), a marker for reactive oxygen species [Ohinata et al., 2000a] and a potent vasoconstrictor, raising the possibility that 8-iso-PGF(2alpha) may be responsible for noise-induced reductions in cochlear blood flow (CBF). To test this hypothesis, CBF was assessed in the guinea pig in response to 'local' (via the anterior inferior cerebellar artery) and systemic (i.v.) delivery of 8-iso-PGF(2alpha) using laser Doppler flowmetry. Local 8-iso-PGF(2alpha) induced a clear reduction in CBF. With systemic infusion, vascular conductance (VC), the ratio of CBF to systemic blood pressure, decreased in a dose-dependent manner up to 30%, consistent with an 8-iso-PGF(2alpha)-induced constriction of the cochlear vasculature. Infusion of SQ29548, a specific antagonist of 8-iso-PGF(2alpha), appropriately blocked an 8-iso-PGF(2alpha)-induced CBF response. Similarly, noise-induced changes in CBF and VC were prevented by infusion of SQ29548 during noise exposure or by antioxidant treatment (glutathione monoethyl ester) prior to exposure. Prevention of isoprostane-mediated vasoconstriction may have clinical utility in the protection from noise-induced hearing loss.
