Endothelial influences on cerebrovascular tone

Andresen, Jon; Shafi, Nadeem I.; Bryan, Robert M.

doi:10.1152/japplphysiol.00937.2005

Cited by 204 publications

(210 citation statements)

References 206 publications

(180 reference statements)

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“…While the systemic hemodynamic indices are not direct measures of cerebral vascular disturbance, the fact that they significantly associated with neurocognitive and MRI abnormalities suggests that they have the potential to serve as proxy measures of cerebrovascular health. Wall thickening of the carotid artery (IMT), decreased vascular reactivity on tests of flow-mediated dilation (BAR), and, more generally, vessel stiffening provides evidence of diminished integrity of systemic vascular structure and function, including the possibility of endothelial or vascular smooth muscle dysfunction (Andresen, Shari, & Bryan, 2006;Hassan et al, 2004;Lavi, Gaitini, Milloul, & Jacob, 2006;Panza, Casino, Kilcoyne, & Quyyumi, 1993). Among people with severe CVD, the effects of these systemic abnormalities on the brain would be compounded in the context of diminished or unstable cardiac function.…”

Section: Discussionmentioning

confidence: 99%

Vascular and cognitive functions associated with cardiovascular disease in the elderly

Cohen

Poppas

Forman

et al. 2008

Journal of Clinical and Experimental Neuropsychology

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This study examines the relationship between systemic vascular function, neurocognitive performance, and structural brain abnormalities on magnetic resonance imaging (MRI) among geriatric outpatients with treated, stable cardiovascular disease and no history of neurological illness (n = 88, ages 56-85 years). Vascular function was assessed by cardiac ejection fraction and output, sequential systolic and diastolic blood pressures, flow mediated brachial artery reactivity (BAR), and carotid intima media thickness (IMT). White matter hyperintensities (WMH) on MRI were quantified and examined relative to cognitive and vascular function. Principal component analysis revealed two primary vascular components: one associated with cardiac function, the other with atherosclerotic burden/endothelial dysfunction. Both factors were significantly associated with cognitive function and WMH volume. Reduced systolic variability and increased IMT were most strongly related to reduced attention, executive function, and information-processing speed. These findings suggest the possibility that systemic vascular indices may provide proxy measures of cerebrovascular dysfunction and reinforce the importance of achieving greater understanding of interaction between systemic vascular disease and brain dysfunction among elderly people with cardiovascular disease.Address correspondence to Ronald A. Cohen, Centers for Behavioral and Preventive Medicine, The CORO Building, 5th Floor, One Hoppin Street, Providence, RI 02903, USA (RCohen@lifespan.org). Vascular cognitive impairments (VCI) occur on a continuum ranging from mild deficits among patients with vascular risk factors such as cardiovascular disease (CVD) to the severe cognitive dysfunction characteristic of vascular dementia (Bowler, Steenhuis, & Hachinski, 1999;Rockwood, 2002;Roman, Erkinjuntti, Wallin, Pantoni, & Chui, 2002). Cardiovascular disease was once thought to convey little risk to the brain given its capacity for vascular autoregulation and sustained cerebral perfusion even under adverse hemodynamic conditions (Lassen, 1964). Brain dysfunction secondary to cardiovascular disease was usually attributed to acute stroke during cardiac surgery (Newman et al., 2001), or in response to cardiac events (e.g., arrhythmia). Yet, patients with severe cardiovascular disease frequently exhibit cognitive problems in the absence of clinically identified stroke (Moser et al., 1999;Paul et al., 2005), particularly in cases of heart failure (Bennett & Sauve, 2003;Bornstein, Starling, Myerowitz, & Haas, 1995), presumably reflecting the impact of reduced cardiac function on the aging brain (Roman, 2004). We have previously shown that both cognitive dysfunction and structural brain abnormalities on magnetic resonance imaging (MRI) are associated with reduced cardiac output among patients with severe cardiovascular disease (Jefferson, Poppas, Paul, & Cohen, 2007a;Jefferson et al., 2007b) and abnormalities of systemic vascular function (Gunstad et al., 2006a;Gunstad et al., 2005;Gunstad e...

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Section: Discussionmentioning

confidence: 99%

Vascular and cognitive functions associated with cardiovascular disease in the elderly

Cohen

Poppas

Forman

et al. 2008

Journal of Clinical and Experimental Neuropsychology

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“…The extracted NT-CNP was added to primary rabbit antiserum (J39) raised against NT-proCNP-(1-15) (1:6,000 dilution, 100 l antiserum/assay tube). Peptide standards were made from synthetic human proCNP- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), with the purity data supplied by the manufacturer (Chiron Technologies) taken into account. Within-and between-assay CVs were 6.0% and 7.9%, respectively.…”

Section: Analytic Measurementsmentioning

confidence: 99%

“…NO, synthesized from the terminal guanidino nitrogen atom(s) of L-arginine in a two-step reaction that is catalyzed by the enzyme NO synthase (NOS) (48), is an important vasoactive factor that dilates the cerebral vasculature. Under normal conditions, two isoforms of NOS are expressed in the brain, endothelium-derived NOS (eNOS) and neuronal-derived NOS (nNOS) (61), although evidence for the role of eNOS vs. nNOS in the control of CBF is controversial (3). Vasodilation evoked by NO is initiated by an increase in cGMP (7).…”

mentioning

confidence: 99%

“…Although other local factors may also influence CBF during such changes in arterial blood gases (3,6,9), the aforementioned vasoactive factors, including NO (as indexed by nitrite), are reliably quantifiable in human blood. Surprisingly, however, none of these vasoactive substances have been sampled across the human brain during controlled changes in arterial blood gases.…”

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confidence: 99%

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Human cerebral arteriovenous vasoactive exchange during alterations in arterial blood gases

Peebles

Richards²,

Celi

et al. 2008

Journal of Applied Physiology

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Evidence from animal studies indicates that various vasoactive factors, including release of norepinephrine, endothelin, adrenomedullin, C-natriuretic peptide (CNP), and nitric oxide (NO), may play a role in arterial blood gas-induced alterations in CBF. For the first time, we directly quantified exchange of these vasoactive factors across the human brain. Using the Fick principle and transcranial Doppler ultrasonography, we measured CBF in 12 healthy humans at rest and during hypercapnia (4 and 8% CO 2), hypocapnia (voluntary hyperventilation), and hypoxia (12 and 10% O 2). At each level, blood was sampled simultaneously from the internal jugular vein and radial artery. With the exception of CNP and NO, the simultaneous quantification of norepinephrine, endothelin, or adrenomedullin showed no cerebral uptake or release during changes in arterial blood gases. Hypercapnia, but not hypocapnia, increased CBF and caused a net cerebral release of nitrite (a marker of NO), which was reflected by an increase in the venous-arterial difference for nitrite: 57 Ϯ 18 and 150 Ϯ 36 mol/l at 4% and 8% CO 2, respectively (both P Ͻ 0.05). Release of cerebral CNP was also observed during changes in CO 2 (hypercapnia vs. hypocapnia, P Ͻ 0.05). During hypoxia, there was a net cerebral uptake of nitrite, which was reflected by a decreased venous-arterial difference for nitrite: Ϫ96 Ϯ 14 mol/l at 10% O 2 (P Ͻ 0.05). These data indicate that there is a differential exchange of NO across the brain during hypercapnia and hypoxia and that CNP may play a complementary role in CO 2-induced CBF changes. cerebral circulation; nitric oxide; endothelium RESPIRATORY-INDUCED CHANGES in arterial PCO 2 (Pa CO 2 ) and, to a lesser extent, PO 2 (Pa O 2 ) play a major role in cerebral blood flow (CBF) regulation (9). Elevations in Pa CO 2 (hypercapnia) lead to vasodilation of cerebral arterioles in the downstream bed and a subsequent increase in CBF, whereas a reduction in Pa CO 2 (hypocapnia) leads to vasoconstriction and a subsequent decrease in CBF (28, 65). A fall in Pa O 2 (hypoxia) below a certain threshold (Ͻ40 Torr) also produces cerebral vasodilation (19). These arterial blood gas-induced changes in CBF are mediated through changes in cerebrovascular resistance via alterations in vascular smooth muscle diameter in response to changes in the level of intracellular calcium and/or calcium sensitivity (for review see Ref. 22). Cerebrovascular tone is influenced by several chemical substances, including nitric oxide (NO). NO, synthesized from the terminal guanidino nitrogen atom(s) of L-arginine in a two-step reaction that is catalyzed by the enzyme NO synthase (NOS) (48), is an important vasoactive factor that dilates the cerebral vasculature. Under normal conditions, two isoforms of NOS are expressed in the brain, endothelium-derived NOS (eNOS) and neuronal-derived NOS (nNOS) (61), although evidence for the role of eNOS vs. nNOS in the control of CBF is controversial (3). Vasodilation evoked by NO is initiated by an increase in cGMP (7).Pharmac...

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“…Various mediators of constriction have been advanced: irritation from hemoglobin or breakdown products of hemoglobin, including bilirubin oxidation products (BOXes) and other reactive oxygen species; binding of nitric oxide (NO) by hemoglobin; production of endothelin-1 by damaged endothelium; generation of 20-hydroxyeicosatetraeonic acid (20-HETE) from arachidonic acid; infiltration of the vessel wall by inflammatory cells resulting in vessel narrowing; and manipulation of cerebral vessels during surgical intervention to clip the ruptured aneurysm. [5][6][7][8] The premise of ''triple-H'' therapy (hypertension, hypervolemia, and hemodilution), which remains a cornerstone of management of intractable cerebral vasospasm, is that ischemia will be relieved by overpowering vessel vasoconstriction by a greater perfusion pressure. 2,9,10 Indeed, this combination therapy can be therapeutic in a significant proportion of patients but often at a cost, especially in the elderly with the potential or reality of myocardial ischemia, pulmonary edema, or renal compromise.…”

Section: Historical Mechanismsmentioning

confidence: 99%

New concepts regarding cerebral vasospasm: glial-centric mechanisms

Mutch

2010

Can J Anesth/J Can Anesth

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Purpose Poor outcome in patients with cerebral vasospasm following subarachnoid hemorrhage remains a serious clinical problem. The current management with focus on the cerebrovascular constriction accounts for the use of ''triple-H'' therapy (hypertension, hypervolemia, and hemodilution) to enhance cerebral blood flow through constricted vessels. Recent work suggests that spreading depression (a stereotypical response of cerebral cortical tissue to noxious stimuli with subsequent oligemic blood flow) occurs in patients with cerebral vasospasm. A narrative review was conducted to examine the relationship between spreading depression and subarachnoid hemorrhage and to identify the anesthetic effects on the propagation of spreading depression. Principal findings Following review of the literature, an underlying mechanism is advanced that cerebral vasospasm is not primarily a problem of the cerebral vasculature but a consequence of glial cell dysfunction following spreading depression -a glial-centric cause for vasospasm. Such a mechanism for vasospasm becomes manifest when spreading depression waves transition to peri-infarct depolarization waves -with protracted ischemic blood flow in compromised tissue. The extracellular microenvironment with high potassium and low nitric oxide tension can account for conducting vessel narrowing. Conclusions The implication for clinical management is discussed supposing glial cell dysfunction is an underlying mechanism responsible for the vascular spasm. RésuméObjectif Les mauvais pronostics chez les patients manifestant un vasospasme ce´re´bral a`la suite d'une he´morragie sous-arachnoı¨dienne demeurent un proble`me clinique majeur. La prise en charge actuelle se concentre sur la constriction vasculaire ce´re´brale, ce qui explique le recours au traitement dit des « trois H » (hypertension, hypervole´mie et he´modilution) dans le but d'ame´liorer le de´bit sanguin ce´re´bral dans les vaisseaux contracte´s. Des recherches re´centes sugge`rent qu'une de´pression propage´e (une re´action typique du tissu cortical ce´re´bral aux stimuli nociceptifs, laquelle est suivie d'un de´bit sanguin re´duit) survient chez les patients manifestant un vasospasme ce´re´bral. Un compte-rendu narratif a e´te´entrepris afin d'examiner la relation entre la de´pression propage´e et l'he´morragie sous-arachnoı¨dienne ainsi que d'identifier les effets des anesthe´siques sur la propagation de la de´pression propage´e. Constatations principales Apre`s avoir passe´en revue la litte´rature sur le sujet, l'hypothe`se d'un me´canisme sous-jacent est avance´e, selon laquelle le vasospasme ce´re´bral n'est pas un proble`me principalement lie´a`la vasculature ce´re´brale mais plutôt la conse´quence d'un dysfonctionnement des cellules gliales apre`s une de´pression propage´e -en d'autres mots, le vasospasme est cause´principalement au niveau glial. Ce me´canisme qui provoque le vasospasme est manifeste lorsque les vagues de de´pression propage´e se changent en vagues de de´polarisation autour de l'infarct...

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Endothelial influences on cerebrovascular tone

Cited by 204 publications

References 206 publications

Vascular and cognitive functions associated with cardiovascular disease in the elderly

Vascular and cognitive functions associated with cardiovascular disease in the elderly

Human cerebral arteriovenous vasoactive exchange during alterations in arterial blood gases

New concepts regarding cerebral vasospasm: glial-centric mechanisms

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