Potential clinical application of recently discovered brain mechanisms involved in hypertension.

The aim of this review is to inform clini-cians about the involvement of brain mechanisms in clinical hypertension and the applicability of recent findings to clinical practice. Clinicians, particularly cardiologists and nephrolo-gists, 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. 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 sym-pathoinhibitory action lasts for a much longer period than previously thought, without rapid adaptation. In addition, the currently used antihypertensive drugs are suggested to act on the central nervous system. The brain is essential for processing and integrating various stimuli from the periphery to maintain blood pressure and fluid homeostasis. The circumventricular organs, hypo-thalamus, 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). 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. 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 aor-tic 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 level remained above control levels. 15 Lohmeier et al 12,13 subsequently observed that …