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

Abstract

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 b 2 -adrenergic receptor (b 2 -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 b 2 -AR expression in the lower brainstem were analyzed by western blot analyses. In the leukocytes, TH and b 2 -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 b 2 -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 b 2 -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 b 2 -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 b 2 -AR in leukocytes from SHR to similar levels of those of WKY. Our study demonstrated that the percentage of leukocytes expressing TH and b 2 -AR was altered in arterial hypertension and can be modulated by central sympathetic inhibition with clonidine treatment.

Catecholaminergic axon innervation and morphology in flat‐mounts of atria and ventricles of mice

“…Using our approach would be valuable for future quantitative studies to further investigate the regional differences of TH‐IR axon innervation in the heart and the interaction with different cardiac targets. Additionally, considering the role of TH as a key enzyme in the synthesis of catecholamines, its alteration is associated with pathological conditions, including CVDs (hypertension, heart failure, myocardial infarction, and atrial fibrillation) (Li et al., 2013; Nisimura et al., 2020), and sleep breathing disorders like sleep apnea (Bathina et al., 2013). Therefore, basic knowledge of the normal anatomical structure of cardiac TH‐IR axon innervation is a crucial step for establishing a baseline to use when evaluating potential remodeling induced by different pathological conditions.…”

“…Our work demonstrated the large-scale morphological and distribution characteristics of catecholaminergic innervation in the atria and ventricles and established a flat-mount approach to investigate detailed cardiac neuroanatomy in future studies. Using our approach would be valuable for future quantitative studies to further investigate the (hypertension, heart failure, myocardial infarction, and atrial fibrillation) (Li et al, 2013;Nisimura et al, 2020), and sleep breathing disorders like sleep apnea (Bathina et al, 2013). Therefore, basic knowledge of the normal anatomical structure of cardiac TH-IR axon innervation is a crucial step for establishing a baseline to use when evaluating potential remodeling induced by different pathological conditions.…”

The Potential Regenerative Effect of L-carnitine Pretreated Mesenchymal Stem Cells in Myocardial Infarction Through Modulating Apoptosis, Inflammation, and Cellular Differentiation

“…TH regulates the rate of catecholamine synthesis. It is essential for heart function, particularly under stress conditions [83]. TH is a cardiac muscle differentiation that is evident in the initial stages of heart development, especially in gastrulation.…”

Serum Amino Acid Levels and Mortality in Patients Undergoing Percutaneous Endoscopic Gastrostomy

“…Therefore, it is an important part of the body's sympathetic nervous system. 21 People who are under stress need more tyrosine. Tyrosine supplementation in these individuals increases the resistance of the metabolism against stress by preventing depletion of norepinephrine.…”