Role of Nitric Oxide in the Regulation of Cerebral Blood Flow in Humans

Lavi, Shahar; Egbarya, Rania; Lavi, Ron; Jacob, Giris

doi:10.1161/01.cir.0000057973.99140.5a

Cited by 121 publications

(129 citation statements)

References 44 publications

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“…SNP reduces SVR, but when infused directly in the carotid artery, it does not modify cerebrovascular resistance in healthy subjects. 41 These findings, together with recent evidence that in normotensive subjects a reduction in MAP by SNP does not affect MCA V mean , 32 suggest that when BP is reduced pharmacologically, MCA V is secured by CA-mediated cerebral vasodilatation rather than a direct SNP-induced pharmacological effect on the cerebral vasculature. The present data demonstrate systemic vasodilatation during SNP treatment with a considerable increase in CO but no change in the cerebrovascular conductance index.…”

Section: Snp and Cerebral Hemodynamicsmentioning

confidence: 89%

“…Third, in the reference subjects, we did not determine MCA V during a substantial decrease in BP induced by SNP infusion; thus, sCA was not evaluated. We consider that, in healthy subjects, a decline in MAP induced by SNP of Ϸ20% barely affects MCA V mean , 32 and CBF, 15 whereas a reduction in mean IAP in the patients was associated with a significant decline in MCA V mean . In addition, in healthy subjects, data on dCA reflect the integrity of sCA 33 , and we assume sCA to be preserved in the reference subjects.…”

Section: Study Limitationsmentioning

confidence: 99%

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Impaired Cerebral Autoregulation in Patients With Malignant Hypertension

et al. 2004

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Background-In patients with a malignant hypertension, immediate parenteral treatment with blood pressure-lowering agents such as intravenous sodium nitroprusside (SNP) is indicated. In this study, we evaluated static and dynamic cerebral autoregulation (CA) during acute blood pressure lowering with SNP in these patients. Methods and Results-In 8 patients with mean arterial pressure (MAP) Ͼ140 mm Hg and grade III or IV hypertensive retinopathy at hospital admission, middle cerebral artery blood velocity (MCA V) and blood pressure were monitored. Dynamic CA was expressed as the 0.1-Hz MCA V mean to MAP phase lead and static CA as the MCA V mean to MAP relationship during SNP treatment. Eight normotensive subjects served as a reference group. In the patients, the MCA V mean to MAP phase lead was lower (30Ϯ8°versus 58Ϯ5°, meanϮSEM; PϽ0.05), whereas the transfer gain tended to be higher. During SNP treatment, target MAP was reached within 90 minutes in all patients. The MCA V mean decrease was 22Ϯ4%, along with a 27Ϯ3% reduction in MAP (from 166Ϯ4 to 121Ϯ6 mm Hg; PϽ0.05) in a linear fashion (averaged slope, 0.82Ϯ0.15% cm · s Ϫ1 · % mm Hg

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Section: Snp and Cerebral Hemodynamicsmentioning

confidence: 89%

Section: Study Limitationsmentioning

confidence: 99%

Impaired Cerebral Autoregulation in Patients With Malignant Hypertension

et al. 2004

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“…Conversely, in rodents, neuronal NO was the more important source (47). Collectively, although the precise contribution of eNOS and nNOS during hypercapnia is unclear (45), previous animal and human studies indicate that eNOS is an important, although not exclusive, mediator of hypercapnia-induced alterations in CBF in healthy young humans (36). It should be noted that the index of NO used in the present study was confined to eNOS, yet the observed increase in CBF represents a collective response.…”

Section: Pa Co 2 and Nitrite Exchangementioning

confidence: 95%

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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“…18 This phenomenon is known as the cerebrovascular CO 2 responsiveness and reflects the vasodilatatory capacity of the cerebral vasculature or cerebrovascular reserve capacity. [19][20][21][22] A reduced cerebrovascular reserve capacity has been demonstrated to be an independent predictor of cerebrovascular ischemic events. [23][24][25] Cerebrovascular CO 2 responsiveness has been demonstrated to be impaired in patients with endothelial dysfunction and cerebral microangiopathy, possibly the result of a reduced NO bioavailability.…”

Section: ;114:3473-3478) Introductionmentioning

confidence: 99%

Cerebrovascular reserve capacity is impaired in patients with sickle cell disease

Nur

Kim

Truijen

et al. 2009

Blood

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Sickle cell disease (SCD) is associated with a high incidence of ischemic stroke. SCD is characterized by hemolytic anemia, resulting in reduced nitric oxidebioavailability, and by impaired cerebrovascular hemodynamics. Cerebrovascular CO 2 responsiveness is nitric oxide dependent and has been related to an increased stroke risk in microvascular diseases. We questioned whether cerebrovascular CO 2 responsiveness is impaired in SCD and related to hemolytic anemia. Transcranial Doppler-determined mean cerebral blood flow velocity (V mean ), near-infrared spectroscopy-determined cerebral oxygenation, and end-tidal CO 2 tension were monitored during normocapnia and hypercapnia in 23 patients and 16 control subjects. Cerebrovascular CO 2 responsiveness was quantified as ⌬% V mean and ⌬mol/L cerebral oxyhemoglobin, deoxyhemoglobin, and total hemoglobin per mm Hg change in end-tidal CO 2 tension. Both ways of measurements revealed lower cerebrovascular CO 2 responsiveness in SCD patients versus controls (V mean , 3.7, 3.1-4.7 vs 5.9, 4.6-6.7 ⌬% V mean per mm Hg, P < .001; oxyhemoglobin, 0.36, 0.14-0.82 vs 0.78, 0.61-1.22 ⌬mol/L per mm Hg, P ‫؍‬ .025; deoxyhemoglobin, 0.35, 0.14-0.67 vs 0.58, 0.41-0.86 ⌬mol/L per mm Hg, P ‫؍‬ .033; total-hemoglobin, 0.13, 0.02-0.18 vs 0.23, 0.13-0.38 ⌬mol/L per mm Hg, P ‫؍‬ .038). Cerebrovascular CO 2 responsiveness was not related to markers of hemolytic anemia. In SCD patients, impaired cerebrovascular CO 2 responsiveness reflects reduced cerebrovascular reserve capacity, which may play a role in pathophysiology of stroke. (Blood. 2009;114:3473-3478) IntroductionCerebral infarction is one of the most devastating complications of sickle cell disease (SCD), occurring in approximately 10% of patients in the first 2 decades of life. 1-3 Furthermore, silent cerebral infarctions occur in approximately 17% of pediatric patients 4,5 and are associated with poor educational and cognitive functioning. 6 SCD is characterized by chronic hemolytic anemia and ongoing vaso-occlusion with exacerbations often requiring medical care. [7][8][9] The vaso-occlusive process in SCD is of a complex nature mediated by red cell and leukocyte adhesion, inflammation, oxidative stress, and a hypercoagulable state, all resulting in endothelial injury and dysfunction. 8 In addition, by reducing the nitric oxide (NO) bioavailability and by damaging the endothelium through the catalyzation of oxidative reactions in endothelial cells, chronic hemolysis leads to vascular complications. [10][11][12] Elevated cerebral blood flow (CBF) velocity (Ն 200 cm/s), measured by transcranial Doppler (TCD), has been identified as a risk factor for stroke in SCD. 13 However, little is known about the mechanism of (ischemic) stroke in SCD patients, and it has not been elucidated whether the increased CBF velocity plays a causative role in stroke or whether it is a result of SCD-related hemodynamic disturbances.CBF is tightly regulated to maintain constancy of cerebral perfusion in the face of various systemic blood pressures by both ...

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Role of Nitric Oxide in the Regulation of Cerebral Blood Flow in Humans

Cited by 121 publications

References 44 publications

Impaired Cerebral Autoregulation in Patients With Malignant Hypertension

Impaired Cerebral Autoregulation in Patients With Malignant Hypertension

Human cerebral arteriovenous vasoactive exchange during alterations in arterial blood gases

Cerebrovascular reserve capacity is impaired in patients with sickle cell disease

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