title: 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 microliters 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, NG-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.
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor 48109-0506, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Vass
authors.forename: P B
authors.initials: PB
authors.lastname: Brechtelsbauer
authors.forename: A L
authors.initials: AL
authors.lastname: Nuttall
authors.forename: J M
authors.initials: JM
authors.lastname: Miller
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000633:toxicity*; D003051:Cochlea / Q000098:blood supply* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D007275:Injections, Intravenous; D017078:Laser-Doppler Flowmetry; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000633:toxicity*; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D013373:Substance P / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D013373:Substance P; D019001:Nitric Oxide Synthase; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester