Nitric oxide mediates capsaicin-induced increase in cochlear blood flow

Abstract

Capsaicin has been previously shown to increase cochlear blood flow (CBF) in a dose-dependent manner. The aim of this study was to define the role of nitric oxide (NO) in capsaicin-induced changes in CBF. This was investigated in the anesthetized guinea pig, utilizing laser Doppler flowmetry. Application of capsaicin (64.8 and 6.48 nmol in 2 μl of 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) reduced blood flow in the cochlea, as previously reported. After pretreatment 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 CBF 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 application also decreased the capsaicin vasodilatation effect. A capsaicin dose of 64.8 nmol resulted in only a 10 ± 2.5% BL increase in CBF, and with 6.48 nmol capsaicin the increase was 7.8 ± 2.2% of BL ( P < 0.001). Capsaicin-sensitive sensory neurons in other systems are generally known to release substance P (SP), which in turn elicits release of endothelium derived relaxing factor (NO). The results of this study indicate that NO is a mediator of capsaicin-sensitive sensory neuronal function in CBF regulation.