Neurogenic Hypertension and Elevated Vertebrobasilar Arterial Resistance: Is There a Causative Link?

Cates, Matthew; Dickinson, C. J.; Hart, Emma C J; Paton, Julian F. R.

doi:10.1007/s11906-012-0267-6

Cited by 45 publications

(67 citation statements)

References 85 publications

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“…Evidence in animals and humans now suggest that this theory may be incorrect with the reverse true; cerebral artery remodeling and hypoperfusion may precede hypertension as found herein. 10,11 Remarkably, in this study, we show that cerebral vascular resistance is increased before the onset of sympathetic hyperactivity and hypertension in humans. Cerebral vascular resistance was elevated in a group of participants with borderline-high BP (daytime systolic BP: 130-135 mm Hg), as it was in all other hypertensive groups, whereas the level of SNA in the borderline population was similar to age-matched controls.…”

Section: Discussionsupporting

confidence: 57%

“…This has been termed Cushing's mechanism or the selfish brain hypothesis of hypertension. 11 The mechanism may trigger elevations in SNA and BP, thereby maintaining cerebral blood flow. 8,12 Evidence from spontaneously hypertensive rats at a prehypertensive age supports this notion : Cates et al 8 demonstrated that vertebrobasilar artery hypertrophy occurred before the onset of hypertension in these animals.…”

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confidence: 99%

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Is High Blood Pressure Self-Protection for the Brain?

Warnert

Rodrigues

Burchell

et al. 2016

Circulation Research

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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:

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Section: Discussionsupporting

confidence: 57%

mentioning

confidence: 99%

Is High Blood Pressure Self-Protection for the Brain?

Warnert

Rodrigues

Burchell

et al. 2016

Circulation Research

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“…The high activity of C1 cells present in vivo could possibly be partly intrinsic to these neurons, perhaps of dendritic origin, or it could be under the control of unconventional and as yet unidentified transmitters (66,76). The basal discharge rate of various subsets of C1 cells could be regulated, directly or via the glia, by local factors such as hypoxia, hypoglycemia, inflammatory cytokines (IL1), blood flow restriction, and circulating steroid hormones (32,146,163).…”

Section: C1 Cells Hypotension and Baroreflexesmentioning

confidence: 99%

“…The "selfish brain hypothesis" of hypertension is a variation on the theme of the Cushing response (32). The idea is that flow restriction within the brain stem vasculature, including the VLM and NTS, caused by compression of hypertrophied vessels or by an inflammatory process that reduces the arteriolar lumen, produces local hypoxia or some other biochemical change leading to neuronal activation and ultimately activation of the sympathetic outflow, in other words a graded Cushing response that restores brain blood flow (32). Finally, the activity of the C1 neurons could theoretically be upregulated by a change in their intrinsic properties.…”

Section: C1 Cells and Diseasementioning

confidence: 99%

C1 neurons: the body's EMTs

Guyenet

Stornetta

Bochorishvili

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

248

262

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The C1 neurons reside in the rostral and intermediate portions of the ventrolateral medulla (RVLM, IVLM). They use glutamate as a fast transmitter and synthesize catecholamines plus various neuropeptides. These neurons regulate the hypothalamic pituitary axis via direct projections to the paraventricular nucleus and regulate the autonomic nervous system via projections to sympathetic and parasympathetic preganglionic neurons. The presympathetic C1 cells, located in the RVLM, are probably organized in a roughly viscerotopic manner and most of them regulate the circulation. C1 cells are variously activated by hypoglycemia, infection or inflammation, hypoxia, nociception, and hypotension and contribute to most glucoprivic responses. C1 cells also stimulate breathing and activate brain stem noradrenergic neurons including the locus coeruleus. Based on the various effects attributed to the C1 cells, their axonal projections and what is currently known of their synaptic inputs, subsets of C1 cells appear to be differentially recruited by pain, hypoxia, infection/inflammation, hemorrhage, and hypoglycemia to produce a repertoire of stereotyped autonomic, metabolic, and neuroendocrine responses that help the organism survive physical injury and its associated cohort of acute infection, hypoxia, hypotension, and blood loss. C1 cells may also contribute to glucose and cardiovascular homeostasis in the absence of such physical stresses, and C1 cell hyperactivity may contribute to the increase in sympathetic nerve activity associated with diseases such as hypertension. C1 neurons; blood pressure; brain stem BEST KNOWN for their contribution to the control of arterial pressure (AP), the C1 neurons have also been implicated in many other physiological processes ranging from neuroendocrine responses to infection and inflammation, glucose homeostasis, reproduction, breathing, thermoregulation, hypothalamo-pituitary axis (HPA)-mediated stress responses, and food consumption. The purpose of this review is to summarize the most salient information concerning the C1 cells, to point out some of the remaining gaps in our current knowledge, and to suggest a few unifying physiological principles that could account for these seemingly disparate observations. Based on the various effects attributed to the C1 cells and what is currently known of their synaptic inputs, we propose that these neurons are, figuratively speaking, the body's "emergency medical technicians." By this we imply that these neurons produce stereotyped autonomic, metabolic, and neuroendocrine responses designed to help the organism survive major acute physical stresses such as accidental, pathological, or dive-related hypoxia or physical injury and its associated cohort of acute infection, blood loss, and hypotension. These emergency responses include, in the short term and depending on the stress, vasoconstriction, cardioinhibition, or acceleration, breathing stimulation, antidiuresis, changes in metabolism, and gastrointestinal (GI) functions designed to conserve pe...

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“…In our human study and that of others, successful RDN treatment did not lower SBP to target levels in the majority of patients (<140 mm Hg; 38% at 6 months in Symplicity-1 14 ) or reduce BP to levels that allowed removal of antihypertensive medication. 9,14 Clearly, other factors are involved and may include poor cerebral perfusion, 48,49 excessive carotid body activity, 50,51 activation of the innate immune system, 31,52 and alterations in arterial baroreceptor input.…”

Section: Perspectives: One Size Does Not Fit Allmentioning

confidence: 99%

Translational Examination of Changes in Baroreflex Function After Renal Denervation in Hypertensive Rats and Humans

et al. 2013

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Abstract-Renal denervation has shown promise in the treatment of resistant hypertension, although the mechanisms underlying the blood pressure (BP) reduction remain unclear. In a translational study of spontaneously hypertensive rats (n=7, surgical denervation) and resistant hypertensive human patients (n=8; 5 men, 33-71 years), we examined the relationship among changes in BP, sympathetic nerve activity, and cardiac and sympathetic baroreflex function after renal denervation. In humans, mean systolic BP (SBP; sphygmomanometry) and muscle sympathetic nerve activity (microneurography) were unchanged at 1 and 6 months after renal denervation (P<0.05). Interestingly, 4 of 8 patients showed a 10% decrease in SBP at 6 months, but sympathetic activity did not necessarily change in parallel with SBP. In contrast, all rats showed significant and immediate decreases in telemetric SBP and lumbar sympathetic activity (P<0.05), 7 days after denervation. Despite no change in SBP, human cardiac and sympathetic baroreflex function (sequence and threshold techniques) showed improvements at 1 and 6 months after denervation, particularly through increased sympathetic baroreflex sensitivity to falling BP. This was mirrored in spontaneously hypertensive rats; cardiac and sympathetic baroreflex sensitivity (spontaneous sequence and the Oxford technique) improved 7 days after denervation. The more consistent results in rats may be because of a more complete (>90% reduction in renal norepinephrine content) denervation. We conclude that (1) renal denervation improves BP in some patients, but sympathetic activity does not always change in parallel, and (2) baroreflex sensitivity is consistently improved in animals and humans, even when SBP has not decreased. Determining procedural success will be crucial in advancing this treatment modality.

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Neurogenic Hypertension and Elevated Vertebrobasilar Arterial Resistance: Is There a Causative Link?

Cited by 45 publications

References 85 publications

Is High Blood Pressure Self-Protection for the Brain?

Is High Blood Pressure Self-Protection for the Brain?

C1 neurons: the body's EMTs

Translational Examination of Changes in Baroreflex Function After Renal Denervation in Hypertensive Rats and Humans

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