Blood–brain barrier dysfunction: the undervalued frontier of hypertension

The blood–brain barrier (BBB) constitutes the complex anatomic and physiologic interface between the intravascular compartment and the central nervous system, and its integrity is paramount for the maintenance of the very sensitive homeostasis of the central nervous system. Arterial hypertension is a leading cause of morbidity and mortality. The BBB has been shown to be disrupted in essential hypertension. BBB integrity is important for central autonomic control and this may be implicated in the pathophysiology of hypertension. On the other hand, evidence from experimental studies indicates that BBB disruption can be present in both hypertensive disease and dementia syndromes, suggesting a possibly key position of loss of BBB integrity in the pathophysiological pathways linking arterial hypertension with cognitive decline. Although much still remains to be elucidated with respect to the exact underlying mechanisms, the discovery of novel pathological pathways has changed our understanding of adult dementia and central nervous system disease overall, pointing out—in parallel—new potential therapeutic targets. The aim of this review is to summarize current scientific knowledge relevant to the pathophysiologic pathways that are involved in the disruption of the BBB function and potentially mediate hypertension-induced cognitive impairment. In parallel, we underline the differential cognition-preserving effect of several antihypertensive agents of similar blood pressure-lowering capacity, highlighting the presence of previously under-recognized BBB-protective actions of these drugs.