Human hypertension, sympathetic activity and the selfish brain

Abstract

New Findings r What is the topic of this review?This review article revisits an historical hypothesis that cerebral hypoperfusion, caused by elevated cerebral vascular resistances, causes the onset of high sympathetic nerve activity and hypertension in humans. r What advances does it highlight?The review article highlights new evidence indicating that congenital cerebrovascular abnormalities, namely vertebral artery hypoplasia and an incomplete posterior circle of Willis, may play a role in the onset of hypertension.Despite the harmful consequences of high blood pressure (hypertension; e.g. stroke, renal failure, dementia and even death), the underlying physiological mechanisms that cause the onset of hypertension are poorly understood. The most established finding is that hypertension occurs alongside activation of the sympathetic nervous system, yet exactly what triggers this in humans is ambiguous. This review discusses evidence for elevated sympathetic nerve activity, particularly in human hypertension, and revisits an historical theory regarding the aetiology underlying human hypertension that was proposed by Seymour Kety and John Dickinson in the 1940s-1950s. My research group hypothesizes that elevated sympathetic nerve activity and hypertension develop as a fundamental mechanism to maintain adequate cerebral blood flow, which is now termed Cushing's mechanism or the selfish brain hypothesis. Moreover, it goes against the traditional belief that high cerebrovascular resistance is a consequence of hypertension; we propose that this elevated resistance drives hypertension. This review discusses historical and new evidence in animals and humans supporting this hypothesis. In particular, unique human data indicating a higher prevalence of congenital cerebral vascular abnormalities in hypertension are considered.

Reduced arterial vasodilatation in response to hypoxia impairs cerebral and peripheral oxygen delivery in hypertensive men

“…() also excluded the hypothesis that hypoxia‐induced sympathetic overdrive would restrain CBF. On the other hand, in line with the centenary ideas of Harvey Cushing and ‘the selfish brain hypothesis of hypertension’ (Hart, ), a reduced VA DO 2 in HT and a resulting inadequate cerebral oxygenation could stimulate the brainstem to restore its oxygen supply by sympathoexcitation and in turn hypertension. However, MSNA was not correlated with VA DO 2 or regional and tCBF.…”

The age‐related reduction in cerebral blood flow affects vertebral artery more than internal carotid artery blood flow

“…The study evaluated whether the age‐related decline in CBF affects ICA and VA flow differently as age‐related narrowing of VA may increase sympathetic activity and increase blood pressure according to ‘the selfish brain’ hypothesis of hypertension (Hart, ). In 24‐ versus 70‐year‐old normotensive men, we found an age‐related reduction in VA but not ICA diameter and the decline in VA flow was about four times as large as that in ICA.…”

“…The brain stem is important for regulation of blood pressure and the vasodilatory capacity of the vertebral (VA), but not of the internal carotid artery (ICA) is blunted in hypertension as observed in response to both hypoxia (Fernandes et al ., ) and L‐arginine (Vianna et al ., ). The ‘selfish brain’ hypothesis of hypertension proposes that narrowing of VA may increase sympathetic activity and thereby elevate blood pressure (Hart, ), and Cushing () described an increase in blood pressure in response to cerebral ischaemia. Thus, in hypertensive rats sympathetic activity is increased, perhaps secondary to vascular inflammation that narrows vessels supplying the brain stem (Paton & Waki, ; Cates et al ., ).…”

Phenotypic heterogeneity of obesity‐related brain vulnerability: one‐size interventions will not fit all

“…Apart from being a major risk factor for stroke mortality, hypertension is closely linked with alterations in cerebral circulation. 111 The brain is a highly metabolically demanding organ, receiving 15% of the total cardiac output at rest despite weighing only 2% of body weight. 112,113 With a severely limited ability to intrinsically store energy, the brain is highly dependent on an intact vascular system to provide a continuous supply of oxygen and nutrients while clearing metabolic wastes.…”

“…Blood pressure is also intimately involved in brain function. Apart from being a major risk factor for stroke mortality, hypertension is closely linked with alterations in cerebral circulation . The brain is a highly metabolically demanding organ, receiving 15% of the total cardiac output at rest despite weighing only 2% of body weight .…”