Is High Blood Pressure Self-Protection for the Brain?
BACKGROUND
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.


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
Our data indicate that congenital cerebrovascular variants in the posterior circulation and the associated cerebral hypoperfusion may be a factor in triggering hypertension. Therefore, lowering blood pressure may worsen cerebral perfusion in susceptible individuals.
From the Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, United Kingdom (E.A.H.W., R.G.W.); CardioNomics Research Group, Clinical Research and Imaging Centre (J.C.L.R., A.E.B., S.N., L.E.K.R., N.E.M., A.K.N., J.F.R.P., E.C.H.) and School of Physiology, Pharmacology, and Neuroscience, Biomedical Sciences (J.C.L.R., S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.), University of Bristol, United Kingdom; University Hospitals Bristol NHS Foundation Trust, United Kingdom (S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.); Department of Radiology, University of Calgary, Canada (A.D.H.); and CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, Hotchkiss Brain Institute, Canada (A.D.H.).
Esther A H
EA
Warnert
From the Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, United Kingdom (E.A.H.W., R.G.W.); CardioNomics Research Group, Clinical Research and Imaging Centre (J.C.L.R., A.E.B., S.N., L.E.K.R., N.E.M., A.K.N., J.F.R.P., E.C.H.) and School of Physiology, Pharmacology, and Neuroscience, Biomedical Sciences (J.C.L.R., S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.), University of Bristol, United Kingdom; University Hospitals Bristol NHS Foundation Trust, United Kingdom (S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.); Department of Radiology, University of Calgary, Canada (A.D.H.); and CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, Hotchkiss Brain Institute, Canada (A.D.H.).
Jonathan C L
JC
Rodrigues
From the Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, United Kingdom (E.A.H.W., R.G.W.); CardioNomics Research Group, Clinical Research and Imaging Centre (J.C.L.R., A.E.B., S.N., L.E.K.R., N.E.M., A.K.N., J.F.R.P., E.C.H.) and School of Physiology, Pharmacology, and Neuroscience, Biomedical Sciences (J.C.L.R., S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.), University of Bristol, United Kingdom; University Hospitals Bristol NHS Foundation Trust, United Kingdom (S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.); Department of Radiology, University of Calgary, Canada (A.D.H.); and CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, Hotchkiss Brain Institute, Canada (A.D.H.).
Amy E
AE
Burchell
From the Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, United Kingdom (E.A.H.W., R.G.W.); CardioNomics Research Group, Clinical Research and Imaging Centre (J.C.L.R., A.E.B., S.N., L.E.K.R., N.E.M., A.K.N., J.F.R.P., E.C.H.) and School of Physiology, Pharmacology, and Neuroscience, Biomedical Sciences (J.C.L.R., S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.), University of Bristol, United Kingdom; University Hospitals Bristol NHS Foundation Trust, United Kingdom (S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.); Department of Radiology, University of Calgary, Canada (A.D.H.); and CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, Hotchkiss Brain Institute, Canada (A.D.H.).
Sandra
S
Neumann
From the Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, United Kingdom (E.A.H.W., R.G.W.); CardioNomics Research Group, Clinical Research and Imaging Centre (J.C.L.R., A.E.B., S.N., L.E.K.R., N.E.M., A.K.N., J.F.R.P., E.C.H.) and School of Physiology, Pharmacology, and Neuroscience, Biomedical Sciences (J.C.L.R., S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.), University of Bristol, United Kingdom; University Hospitals Bristol NHS Foundation Trust, United Kingdom (S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.); Department of Radiology, University of Calgary, Canada (A.D.H.); and CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, Hotchkiss Brain Institute, Canada (A.D.H.).
Laura E K
LE
Ratcliffe
From the Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, United Kingdom (E.A.H.W., R.G.W.); CardioNomics Research Group, Clinical Research and Imaging Centre (J.C.L.R., A.E.B., S.N., L.E.K.R., N.E.M., A.K.N., J.F.R.P., E.C.H.) and School of Physiology, Pharmacology, and Neuroscience, Biomedical Sciences (J.C.L.R., S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.), University of Bristol, United Kingdom; University Hospitals Bristol NHS Foundation Trust, United Kingdom (S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.); Department of Radiology, University of Calgary, Canada (A.D.H.); and CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, Hotchkiss Brain Institute, Canada (A.D.H.).
Nathan E
NE
Manghat
From the Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, United Kingdom (E.A.H.W., R.G.W.); CardioNomics Research Group, Clinical Research and Imaging Centre (J.C.L.R., A.E.B., S.N., L.E.K.R., N.E.M., A.K.N., J.F.R.P., E.C.H.) and School of Physiology, Pharmacology, and Neuroscience, Biomedical Sciences (J.C.L.R., S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.), University of Bristol, United Kingdom; University Hospitals Bristol NHS Foundation Trust, United Kingdom (S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.); Department of Radiology, University of Calgary, Canada (A.D.H.); and CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, Hotchkiss Brain Institute, Canada (A.D.H.).
Ashley D
AD
Harris
From the Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, United Kingdom (E.A.H.W., R.G.W.); CardioNomics Research Group, Clinical Research and Imaging Centre (J.C.L.R., A.E.B., S.N., L.E.K.R., N.E.M., A.K.N., J.F.R.P., E.C.H.) and School of Physiology, Pharmacology, and Neuroscience, Biomedical Sciences (J.C.L.R., S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.), University of Bristol, United Kingdom; University Hospitals Bristol NHS Foundation Trust, United Kingdom (S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.); Department of Radiology, University of Calgary, Canada (A.D.H.); and CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, Hotchkiss Brain Institute, Canada (A.D.H.).
Zoe
Z
Adams
From the Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, United Kingdom (E.A.H.W., R.G.W.); CardioNomics Research Group, Clinical Research and Imaging Centre (J.C.L.R., A.E.B., S.N., L.E.K.R., N.E.M., A.K.N., J.F.R.P., E.C.H.) and School of Physiology, Pharmacology, and Neuroscience, Biomedical Sciences (J.C.L.R., S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.), University of Bristol, United Kingdom; University Hospitals Bristol NHS Foundation Trust, United Kingdom (S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.); Department of Radiology, University of Calgary, Canada (A.D.H.); and CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, Hotchkiss Brain Institute, Canada (A.D.H.).
Angus K
AK
Nightingale
From the Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, United Kingdom (E.A.H.W., R.G.W.); CardioNomics Research Group, Clinical Research and Imaging Centre (J.C.L.R., A.E.B., S.N., L.E.K.R., N.E.M., A.K.N., J.F.R.P., E.C.H.) and School of Physiology, Pharmacology, and Neuroscience, Biomedical Sciences (J.C.L.R., S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.), University of Bristol, United Kingdom; University Hospitals Bristol NHS Foundation Trust, United Kingdom (S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.); Department of Radiology, University of Calgary, Canada (A.D.H.); and CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, Hotchkiss Brain Institute, Canada (A.D.H.).
Richard G
RG
Wise
From the Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, United Kingdom (E.A.H.W., R.G.W.); CardioNomics Research Group, Clinical Research and Imaging Centre (J.C.L.R., A.E.B., S.N., L.E.K.R., N.E.M., A.K.N., J.F.R.P., E.C.H.) and School of Physiology, Pharmacology, and Neuroscience, Biomedical Sciences (J.C.L.R., S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.), University of Bristol, United Kingdom; University Hospitals Bristol NHS Foundation Trust, United Kingdom (S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.); Department of Radiology, University of Calgary, Canada (A.D.H.); and CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, Hotchkiss Brain Institute, Canada (A.D.H.).
Julian F R
JF
Paton
From the Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, United Kingdom (E.A.H.W., R.G.W.); CardioNomics Research Group, Clinical Research and Imaging Centre (J.C.L.R., A.E.B., S.N., L.E.K.R., N.E.M., A.K.N., J.F.R.P., E.C.H.) and School of Physiology, Pharmacology, and Neuroscience, Biomedical Sciences (J.C.L.R., S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.), University of Bristol, United Kingdom; University Hospitals Bristol NHS Foundation Trust, United Kingdom (S.N., L.E.K.R., Z.A., J.F.R.P., E.C.H.); Department of Radiology, University of Calgary, Canada (A.D.H.); and CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, Hotchkiss Brain Institute, Canada (A.D.H.). emma.hart@bristol.ac.uk.
Emma C
EC
Hart
D000328:Adult; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000502:physiology*; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003430:Cross-Sectional Studies; D000075222:Essential Hypertension; D005260:Female; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014655:Vascular Resistance / Q000502:physiology
body mass index; human; hypertension; magnetic resonance imaging; pathophysiology