NITRIC-OXIDE MEDIATES CAPSAICIN-INDUCED INCREASE IN COCHLEAR BLOOD-FLOW

Capsaicin has been previously shown to increase cochlear blood flow (C BF) in a dose-dependent manner. The aim of this study was to define th e role of nitric oxide (NO) in capsaicin-induced changes in CBF. This was investigated in the anesthetized guinea pig, utilizing laser Doppl er flowmetry. Application of capsaicin (64.8 and 6.48 nmol in 2 mu l o f saline) to the round window membrane (RWM) caused increases in CBF ( 34+/-2.8% of baseline (BL) and 28+/-2.3% BL, respectively (P <0.001)). Application of the NO synthase inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg intravenously or topically to the RWM) reduc ed blood flow in the cochlea, as previously reported. After pretreatme nt with i.v. L-NAME, the effect of capsaicin on CBF was significantly decreased. With the dose of capsaicin at 64.8 nmol, the increase in CB F fell from 34+/-2.8% BL to 6.9+/-1.5% BL (P <0.001), and at 6.48 nmol it fell from 28+/-2.3% BL to 4.8+/-1.6% BL (P <0.001). RWM L-NAME app lication also decreased the capsaicin vasodilatation effect. A capsaic in dose of 64.8 nmol resulted in only a 10+/-2.5% BL increasein CBF, a nd with 6.48 nmol capsaicin the increase was 7.8+/-2.2% of BL (P <0.00 1). Capsaicin-sensitive sensory neurons in other systems are generally known to release substance P (SP), which;in turn elicits release of e ndothelium derived relaxing factor (NO). The results of this study ind icate that NO is a mediator of capsaicin-sensitive sensory neuronal fu nction in CBF regulation.