Laboratório de Inovações em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
Laboratório de Investigação Cardiovascular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
Braz J Med Biol Res. 2020 Oct 30;53(12):e9615. doi: 10.1590/1414-431X20209615. eCollection 2020.
The sympathetic nervous system (SNS) plays a fundamental role in the pathophysiology of cardiovascular diseases, including primary arterial hypertension. In this study, we aimed to investigate whether the expression of the rate-limiting enzyme in catecholamine synthesis, tyrosine hydroxylase (TH), and the β2-adrenergic receptor (β2-AR) in immune cells from peripheral blood, reflect central SNS activity in spontaneously hypertensive rats (SHR). TH expression in the lower brainstem and adrenal glands and β2-AR expression in the lower brainstem were analyzed by western blot analyses. In the leukocytes, TH and β2-AR expression was evaluated by flow cytometry before and after chronic treatment with the centrally-acting sympathoinhibitory drug clonidine. Western blot analyses showed increased TH and β2-AR expression in the lower brainstem and increased TH in adrenal glands from SHR compared to normotensive Wistar Kyoto rats (WKY). Lower brainstem from SHR treated with clonidine presented reduced TH and β2-AR levels, and adrenal glands had decreased TH expression compared to SHR treated with vehicle. Flow cytometry showed that the percentage of leukocytes that express β2-AR is higher in SHR than in WKY. However, the percentage of leukocytes that expressed TH was higher in WKY than in SHR. Moreover, chronic treatment with clonidine normalized the levels of TH and β2-AR in leukocytes from SHR to similar levels of those of WKY. Our study demonstrated that the percentage of leukocytes expressing TH and β2-AR was altered in arterial hypertension and can be modulated by central sympathetic inhibition with clonidine treatment.
交感神经系统（SNS）在心血管疾病的病理生理学中起着至关重要的作用，包括原发性高血压。在这项研究中，我们旨在研究外周血免疫细胞中儿茶酚胺合成限速酶酪氨酸羟化酶（TH）和β2-肾上腺素能受体（β2-AR）的表达是否反映自发性高血压大鼠（SHR）中枢 SNS 活性。通过 Western blot 分析检测下脑和肾上腺中的 TH 表达，以及下脑的β2-AR 表达。通过流式细胞术在慢性给予中枢性交感神经抑制药物可乐定前后评估白细胞中的 TH 和 β2-AR 表达。Western blot 分析显示，与正常血压的 Wistar Kyoto 大鼠（WKY）相比，SHR 下脑的 TH 和 β2-AR 表达增加，肾上腺的 TH 表达增加。与给予载体的 SHR 相比，给予可乐定的 SHR 下脑的 TH 和 β2-AR 水平降低，肾上腺的 TH 表达降低。流式细胞术显示，表达β2-AR 的白细胞百分比在 SHR 中高于 WKY。然而，表达 TH 的白细胞百分比在 WKY 中高于 SHR。此外，慢性给予可乐定可使 SHR 白细胞中的 TH 和 β2-AR 水平正常化，与 WKY 的水平相似。我们的研究表明，TH 和 β2-AR 表达的白细胞百分比在动脉高血压中发生改变，并且可以通过可乐定治疗的中枢交感神经抑制来调节。
