Tyrosine hydroxylase and β2-adrenergic receptor expression in leukocytes of spontaneously hypertensive rats: putative peripheral markers of central sympathetic activity

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（sympathetic nervous system, SNS）在包括原发性动脉高血压（primary arterial hypertension）在内的心血管疾病的病理生理进程中扮演核心角色。本研究旨在探讨外周血免疫细胞内儿茶酚胺合成的限速酶酪氨酸羟化酶（tyrosine hydroxylase, TH）与β2-肾上腺素能受体（β2-adrenergic receptor, β2-AR）的表达水平，是否能够反映自发性高血压大鼠（spontaneously hypertensive rats, SHR）的中枢交感神经活动。 研究采用蛋白质印迹（Western blot）分析了低位脑干与肾上腺中的TH表达，以及低位脑干中的β2-AR表达；并通过流式细胞术（flow cytometry）检测了经中枢性交感抑制药物可乐定慢性给药前后的白细胞中TH与β2-AR的表达水平。 蛋白质印迹结果显示，与血压正常的Wistar Kyoto大鼠（WKY）相比，自发性高血压大鼠的低位脑干中TH与β2-AR表达上调，肾上腺组织内TH表达水平升高。经可乐定处理的自发性高血压大鼠，其低位脑干内TH与β2-AR水平较赋形剂处理组降低，肾上腺组织内TH表达也出现下降。 流式细胞术检测结果表明，自发性高血压大鼠体内表达β2-AR的白细胞占比高于Wistar Kyoto大鼠（WKY）；但表达TH的白细胞占比则在WKY大鼠中更高。此外，慢性可乐定给药可使自发性高血压大鼠白细胞中TH与β2-AR的表达水平恢复至与WKY大鼠相近的正常水平。 本研究证实，表达TH与β2-AR的白细胞占比在动脉高血压状态下发生异常改变，且可通过可乐定介导的中枢交感抑制进行调控。