Potential Clinical Application of Recently Discovered Brain Mechanisms Involved in Hypertension

Abstract

A ccumulating evidence indicates that central activation of the sympathetic nervous system plays an important role in hypertension. [1][2][3][4][5][6][7][8] The aim of this review is to inform clinicians about the involvement of brain mechanisms in clinical hypertension and the applicability of recent findings to clinical practice. Clinicians, particularly cardiologists and nephrologists, are now initiating clinical treatment of hypertension that targets the sympathetic nervous system using novel techniques, such as catheter-based renal denervation and carotid baroreflex activation therapy.9,10 Renal denervation reduces efferent renal sympathetic activity, thereby decreasing renal tubular sodium reabsorption, supporting renal blood flow, and inhibiting the renin-angiotensin-aldosterone system, which has a blood pressure-lowering effect. In addition, it has been proposed that inhibition of central sympathetic outflow via reduced renal afferent input to the brain leads to a long-term reduction in blood pressure.11 Carotid baroreflex activation therapy reduces blood pressure and central sympathetic outflow, and the sympathoinhibitory action lasts for a much longer period than previously thought, without rapid adaptation. 12,13 In addition, the currently used antihypertensive drugs are suggested to act on the central nervous system. 7,14 Neural Mechanisms Are Re-Emerging as a Pathogenesis and Pathophysiology of HypertensionThe brain is essential for processing and integrating various stimuli from the periphery to maintain blood pressure and fluid homeostasis. 1-3 The circumventricular organs, hypothalamus, and brain stem are major brain regions contributing to this function.2 During the past several decades, however, neural mechanisms, such as arterial baroreflex function, have been considered to be involved in short-term blood pressure regulation, but not in long-term blood pressure control (ie, hypertension).1-4 Arterial baroreceptors adapt and thus cannot provide accurate negative feedback signals to the brain to maintain normal arterial pressure. Importantly, surgical removal of the afferent projections of arterial baroreceptors (sinoaortic denervation) results in a transient increase in arterial pressure but does not lead to chronic hypertension.2 These findings suggest that the renin-angiotensin system and kidney are major contributors to the pathogenesis of hypertension. 1,3,4 Several important series of studies revealed that arterial baroreflexes have a role in long-term blood pressure regulation. First, Thrasher 15 produced chronic unloading of arterial baroreceptors in dogs, in which 1 carotid sinus and the aortic depressor nerve were cut, and the carotid sinus from the remaining innervated region was isolated from the systemic arterial pressure. Baroreceptor unloading was then induced by ligating the common carotid artery proximal to the innervated sinus, which led to an increase in arterial pressure that lasted for several weeks; although the initial increase in arterial pressure was not sustained, the l...

Circulating angiotensin II deteriorates left ventricular function with sympathoexcitation via brain angiotensin II receptor

“…2012; Hirooka et al. 2013). Our recent studies also demonstrated that sympathoinhibition attenuated the LV dysfunction independently of blood pressure reduction in rats with hypertensive heart failure (Honda et al.…”

“…2009; Esler 2010; Malpas 2010; Hirooka et al. 2013; Florea and Cohn 2014). Although the sympathetic activity is modulated and controlled by brain, the mechanism by which brain senses the condition of heart failure from the body and leads to sympathoexcitaion have not been fully understood.…”

The Role of Central Nervous System Mechanisms in Resistant Hypertension

“…While the mechanisms inducing the reduction in NO, bioavailability or impairment NO-mediated vasodilation in hypertension are not entirely understood, supportive evidence from experimental models is indicative of a bidirectional interaction between NO and SNS in modulating BP levels [61]. Accordingly, central production of oxidative stress in autonomic brain regions, particularly in the RVLM, increases central sympathetic activation thereby triggering BP elevation [64]. In this context, a better understanding of brain mechanisms linking oxidative stress to human neurogenic hypertension may help to implement novel therapies for drug-RH.…”

Obesity-Associated Hypertension

“…A wealth of information regarding the neuronal mechanisms that contribute to obesity-associated hypertension and sympathetic overdrive have been gathered in recent years (31). In particular, the brain melanocortinergic system has emerged as a crucial molecular pathway in the development of hypertension and other cardiovascular disorders in human obesity.…”