Neurogenic Hypertension, the Blood-Brain Barrier, and the Potential Role of Targeted Nanotherapeutics

Abstract

Hypertension is a major health concern globally. Elevated blood pressure, initiated and maintained by the brain, is defined as neurogenic hypertension (NH), which accounts for nearly half of all hypertension cases. A significant increase in angiotensin II-mediated sympathetic nervous system activity within the brain is known to be the key driving force behind NH. Blood pressure control in NH has been demonstrated through intracerebrovascular injection of agents that reduce the sympathetic influence on cardiac functions. However, traditional antihypertensive agents lack effective brain permeation, making NH management extremely challenging. Therefore, developing strategies that allow brain-targeted delivery of antihypertensives at the therapeutic level is crucial. Targeting nanotherapeutics have become popular in delivering therapeutics to hard-to-reach regions of the body, including the brain. Despite the frequent use of nanotherapeutics in other pathological conditions such as cancer, their use in hypertension has received very little attention. This review discusses the underlying pathophysiology and current management strategies for NH, as well as the potential role of targeted therapeutics in improving current treatment strategies.

Keywords: Angiotensin; antihypertensive; blood–brain barrier; drug-resistant hypertension; lipid-based nanoparticles; nanotherapeutics; neurogenic hypertension; polymer-based nanoparticles; sympathetic nervous activity.

Figure 1

Brain regions that contribute to neurogenic hypertension. Purple stars indicate regions of the circumventricular organs.

Figure 2

Renin–angiotensin system influence on blood pressure. ACE; Angiotensin Converting Enzyme.

Figure 3

Current nanoparticles explored for neurogenic hypertension management. SLN; solid lipid nanoparticles, NLC; nanostructured lipid carriers.