Department of Otolaryngology/Head and Neck Surgery, Oregon Hearing Research Center, Oregon Health and Science University, Portland, Oregon 97239-3098, USA.
Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1248-54. doi: 10.1152/ajpheart.00315.2011. Epub 2011 Aug 19.
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.
内耳中的声音转导需要严格控制氧气和葡萄糖的输送。然而，区域血流控制的机制尚未完全理解。在这项研究中，我们报告了一种新的局部控制机制，该机制调节耳蜗内的血管纹的血液流动，血管纹是内耳高耗能区域。我们发现，细胞外乳酸在体外和体内条件下对螺旋韧带的毛细血管具有血管扩张作用。乳酸通过单羧酸转运蛋白 1（MCT1）起作用，启动神经元型一氧化氮合酶（nNOS）并催化一氧化氮的产生以实现血管扩张。用 MCT 阻滞剂α-氰基-4-羟基肉桂酸（CHC）或通过非特异性一氧化氮合酶抑制剂 N（G）-硝基-L-精氨酸甲酯（L-NAME）或两种选择性 nNOS 抑制剂 3-溴-7-硝基吲唑或（4S）-N-（4-氨基-5[[氨基乙基]氨基]戊基）-N'-硝基胍（TFA）抑制 NO 产生，可完全阻断乳酸引起的血管扩张。用选择性内皮型一氧化氮合酶抑制剂 L-N（5）-（1-亚氨基乙基）鸟氨酸（L-NIO）预处理可消除乳酸诱导的血管扩张抑制。通过免疫组织化学标记，我们发现 MCT1 和 nNOS 在毛细血管偶联型 V 型纤维细胞中表达。数据表明，V 型纤维细胞是乳酸诱导的 NO 的来源。由乳酸调节的耳蜗微血管张力是通过纤维细胞和毛细血管之间的 NO 信号偶联介导的。
