Is High Blood Pressure Self-Protection for the Brain?

Abstract

H igh blood pressure (BP) affects ≈25% of the world's population and is the largest single contributor to global mortality. 1 Hypertension represents a significant economic burden to public healthcare providers, where the global cost of nonoptimal BP is estimated to be US$370 billion (10% of healthcare expenditure). 2Remarkably, despite the availability of many pharmacological treatments, BP is poorly controlled with a recent report stating that only 53% of patients prescribed antihypertensive medication have BP controlled.3 This reflects the well-known heterogeneity of the syndrome, including epigenetic and inherited factors contributing to the unknown causes in 95% of patients. Despite the devastating consequences of hypertension (eg, stroke, kidney failure, coronary heart disease, and death 1,2 ), the mechanisms that lead to the onset of hypertension in humans are poorly understood. It is well established that elevated sympathetic nerve activity (SNA) contributes to the development of hypertension in most humans, [5][6][7] but what initiates this remains unclear. Experimental data from hypertensive rats and observations in postmortem human studies suggest that blood flow to the brain might be important in setting the operating level of SNA and, thus, systemic arterial pressure. Rationale: Data from animal models of hypertension indicate that high blood pressure may develop as a vital mechanism to maintain adequate blood flow to the brain. We propose that congenital vascular variants of the posterior cerebral circulation and cerebral hypoperfusion could partially explain the pathogenesis of essential hypertension, which remains enigmatic in 95% of patients.Objective: To evaluate the role of the cerebral circulation in the pathophysiology of hypertension. Methods and Results:We completed a series of retrospective and mechanistic case-control magnetic resonance imaging and physiological studies in normotensive and hypertensive humans (n=259). Interestingly, in humans with hypertension, we report a higher prevalence of congenital cerebrovascular variants; vertebral artery hypoplasia, and an incomplete posterior circle of Willis, which were coupled with increased cerebral vascular resistance, reduced cerebral blood flow, and a higher incidence of lacunar type infarcts. Causally, cerebral vascular resistance was elevated before the onset of hypertension and elevated sympathetic nerve activity (n=126). Interestingly, untreated hypertensive patients (n=20) had a cerebral blood flow similar to age-matched controls (n=28). However, participants receiving antihypertensive therapy (with blood pressure controlled below target levels) had reduced cerebral perfusion (n=19). Finally, elevated cerebral vascular resistance was a predictor of hypertension, suggesting that it may be a novel prognostic or diagnostic marker (n=126). Conclusions:

Differences in autonomic innervation to the vertebrobasilar arteries in spontaneously hypertensive and Wistar rats

“…These results may explain both the reduced cerebral blood flow and vasodilatory response to increases in metabolic demand in humans with hypertension (Warnert et al . ). Such deficits may increase resistance through this vascular bed and would certainly compromise brainstem blood flow and tissue oxygenation as we found in the SHR brainstem (Marina et al .…”

“…; Warnert et al . ). A reduction in vertebrobasilar artery blood flow resulting from stenosis or remodelling/hypertrophy can trigger a Cushing response (Cushing, ; Rodbard & Stone, ; Schmidt et al .…”

“…In humans, we recently reported hypoplastic vertebrobasilar arteries in hypertensive patients including those with white coat and borderline hypertension suggesting that the remodelling of vertebrobasilar arteries occurs before hypertension develops and most probably is congenital (Warnert et al . ); thus, the remodelling cannot be secondary to the high blood pressure per se . This is supported by the finding that hydralazine treatment of prenatal and postnatal SH rats (SHRs) does not prevent renal artery wall thickening despite a normalisation of blood pressure during treatment (Smeda et al .…”

Noctural dipping status and left ventricular hypertrophy: A cardiac magnetic resonance imaging study

“…Equally, the exaggerated fall in SBP at night may contribute to LVH in extreme dippers. Recently, we demonstrated that increased cerebrovascular resistance and reduced cerebral blood flow were present before the onset of increased muscle sympathetic nerve activity in the borderline hypertensive patients, suggesting cerebral hypoperfusion may be a factor in triggering and exacerbating hypertension . The exaggerated nocturnal drop in BP in extreme dippers could theoretically aggravate nocturnal cerebral perfusion and result in rebound increases in neurogenically‐mediated sympathetic nerve activity.…”

Human hypertension, sympathetic activity and the selfish brain

“…; Warnert et al . ). Vertebral artery hypoplasia is a risk factor for posterior territory stroke (Perren et al .…”