title: Lactate dilates cochlear capillaries via type V fibrocyte-vessel coupling signaled by nNOS.
abstract: Transduction of sound in the inner ear demands tight control over delivery of oxygen and glucose. However, the mechanisms underlying the control of regional blood flow are not yet fully understood. In this study, we report a novel local control mechanism that regulates cochlear blood flow to the stria vascularis, a high energy-consuming region of the inner ear. We found that extracellular lactate had a vasodilatory effect on the capillaries of the spiral ligament under both in vitro and in vivo conditions. The lactate, acting through monocarboxylate transporter 1 (MCT1), initiated neuronal nitric oxide (NO) synthase (nNOS) and catalyzed production of NO for the vasodilation. Blocking MCT1 with the MCT blocker, α-cyano-4-hydroxycinnamate (CHC), or a suppressing NO production with either the nonspecific inhibitor of NO synthase, N(G)-nitro-L-arginine methyl ester (L-NAME), or either of two selective nNOS inhibitors, 3-bromo-7-nitroindazole or (4S)-N-(4-amino-5[aminoethyl]aminopentyl)-N'-nitroguanidine (TFA), totally abolished the lactate-induced vasodilation. Pretreatment with the selective endothelial NO synthase inhibitor, L-N(5)-(1-iminoethyl)ornithine (L-NIO), eliminated the inhibition of lactate-induced vessel dilation. With immunohistochemical labeling, we found the expression of MCT1 and nNOS in capillary-coupled type V fibrocytes. The data suggest that type V fibrocytes are the source of the lactate-induced NO. Cochlear microvessel tone, regulated by lactate, is mediated by an NO-signaled coupling of fibrocytes and capillaries.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Oregon Hearing Research Center, Oregon Health and Science University, Portland, Oregon 97239-3098, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Dai
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Shi
mesh_terms: D000818:Animals; D002196:Capillaries / Q000166:cytology* / Q000187:drug effects*; D003051:Cochlea / Q000098:blood supply* / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007773:Lactates / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D027501:Monocarboxylic Acid Transporters / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000502:physiology*; D020286:Pericytes / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D055493:Spiral Ligament of Cochlea / Q000166:cytology / Q000502:physiology; D027981:Symporters / Q000502:physiology; D059008:Time-Lapse Imaging; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D004791:Enzyme Inhibitors; D007773:Lactates; D027501:Monocarboxylic Acid Transporters; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D027981:Symporters; D014665:Vasodilator Agents; D000099233:Monocarboxylate Transport Protein 1