Background: We previously reported that endothelins (ETs) regulate tyrosine hydroxylase (TH) activity and expression in the olfactory bulb (OB) of normotensive and hypertensive animals. Applying an ET receptor type A (ETA) antagonist to the brain suggested that endogenous ETs bind to ET receptor type B (ETB) to elicit effects. Objective: The aim of the present work was to evaluate the role of central ETB stimulation on the regulation of blood pressure (BP) and the catecholaminergic system in the OB of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Methods: DOCA-salt hypertensive rats were infused for 7 days with cerebrospinal fluid or IRL-1620 (ETB receptor agonist) through a cannula placed in the lateral brain ventricle. Systolic BP (SBP) and heart rate were recorded by plethysmography. The expression of TH and its phosphorylated forms in the OB were determined by immunoblotting, TH activity by a radioenzymatic assay, and TH mRNA by quantitative real-time polymerase chain reaction. Results: Chronic administration of IRL-1620 decreased SBP in hypertensive rats but not in normotensive animals. Furthermore, the blockade of ETB receptors also decreased TH-mRNA in DOCA-salt rats, but it did not modify TH activity or protein expression. Conclusion: These findings suggest that brain ETs through the activation of ETB receptors contribute to SBP regulation in DOCA-salt hypertension. However, the catecholaminergic system in the OB does not appear to be conclusively involved although mRNA TH was reduced. Present and previous findings suggest that in this salt-sensitive animal model of hypertension, the OB contributes to chronic BP elevation.

中文翻译：

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B 型脑内皮素受体 (ETB) 在 DOCA-盐高血压大鼠嗅球酪氨酸羟化酶调节中的作用

背景：我们之前报道内皮素（ET）调节正常血压和高血压动物嗅球（OB）中的酪氨酸羟化酶（TH）活性和表达。将 A 型 ET 受体 (ETA) 拮抗剂应用于大脑表明内源性 ET 与 B 型 ET 受体 (ETB) 结合以产生效应。目的：本研究的目的是评估中枢 ETB 刺激对醋酸去氧皮质酮（DOCA）高血压大鼠产科血压（BP）和儿茶酚胺能系统的调节作用。方法：通过放置在侧脑室的插管向DOCA-盐高血压大鼠注入脑脊液或IRL-1620（ETB受体激动剂）7天。通过体积描记法记录收缩压（SBP）和心率。通过免疫印迹测定 OB 中 TH 及其磷酸化形式的表达，通过放射酶法测定 TH 活性，通过定量实时聚合酶链反应测定 TH mRNA。结果：长期服用 IRL-1620 可降低高血压大鼠的 SBP，但不会降低血压正常动物的 SBP。此外，阻断 ETB 受体也会降低 DOCA 盐大鼠的 TH-mRNA，但不会改变 TH 活性或蛋白质表达。结论：这些研究结果表明，大脑 ET 通过激活 ETB 受体有助于 DOCA 盐高血压中 SBP 的调节。然而，尽管 mRNA TH 减少，但 OB 中的儿茶酚胺能系统似乎并未最终参与其中。目前和之前的研究结果表明，在这种对盐敏感的高血压动物模型中，