Pathophysiology of resistant hypertension: the role of sympathetic nervous system

Costas Tsioufis, Athanasios Kordalis, Dimitris Flessas, Ioannis Anastasopoulos, Dimitris Tsiachris, Vasilios Papademetriou, Christodoulos Stefanadis, Costas Tsioufis, Athanasios Kordalis, Dimitris Flessas, Ioannis Anastasopoulos, Dimitris Tsiachris, Vasilios Papademetriou, Christodoulos Stefanadis

Abstract

Resistant hypertension (RH) is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS) activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge points towards an impact of several factors on SNS activation, namely, insulin resistance, adipokines, endothelial dysfunction, cyclic intermittent hypoxaemia, aldosterone effects on central nervous system, chemoreceptors, and baroreceptors dysregulation. The further investigation and understanding of the mechanisms leading to SNS activation could reveal novel therapeutic targets and expand our treatment options in the challenging management of RH.

Figures

Figure 1
Figure 1
A proposed pathophysiologic pathway for the activation of SNS and the development of RH. Obesity, OSA and aldosterone excess are covering a great area of the mosaic of the phenotype of RH and are correlated with increased SNS activity, via multiple mechanisms. ↑ALDO: Aldosterone excess, OSA: Obstructive sleep apnea, ↑RAAS: Renin-Angiotensin-Aldosterone System activation, RH: Resistant hypertension, ↑SNS: Sympathetic nervous system hyperactivity.

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