Nitrite Infusions to Prevent Delayed Cerebral Vasospasm in a Primate Model of Subarachnoid Hemorrhage

Pluta, Ryszard

doi:10.1001/jama.293.12.1477

Cited by 247 publications

(169 citation statements)

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“…Decreased nitrite levels and their close correlation with development and degree of vasospasm after SAH 39,70,73,76 (Figure 1) further support the hypothesis that decreased NO availability is responsible for or at least significantly contributes to cerebral vasospasm 70 . Reversal and prevention of cerebral vasospasm by NO/NO donors support this hypothesis 2,72 .…”

Section: No and Pathomechanism(s) Of Delayed Cerebral Vasospasmsupporting

confidence: 56%

“…Since the discovery that nitric oxide (NO), an endothelium-derived relaxing factor 22 , has 1000 times higher affinity for hemoglobin than oxygen 52 , neurosurgeons and neuroscientists have been interested in its role in cerebral vasospasm after SAH 2,8,16,44,45,55,[64][65][66]70,87,90,92,94,95,103 . NO influence on blood flow 11,15,99,106,113 , disappearance of neuronal nitric oxide synthase (nNOS) immunoreactivity from the arteries in spasm 75 , endothelial nitric oxide synthase (eNOS) dysfunction in cerebral vessels after SAH 37 , decreased levels of nitrite in the cerebrospinal fluid (CSF) during vasospasm development 40,70,76 , as well NO affinity for the heme moiety 52 together, strongly suggest that decreased availability of NO in the cerebral arterial wall after SAH is responsible for delayed cerebral vasospasm 70 . Recent research has significantly advanced our understanding of the NO-related pathophysiologic changes in the cerebral arteries leading to vasospasm and introduced new possibilities for NO-based therapy for vasospasm 23,76,98 .…”

Section: Introductionmentioning

confidence: 99%

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Dysfunction of nitric oxide synthases as a cause and therapeutic target in delayed cerebral vasospasm after SAH

Pluta

2006

Neurological Research

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Nitric oxide (NO), also known as endothelium-derived relaxing factor, is produced by endothelial nitric oxide synthase (eNOS) in the intima and by neuronal nitric oxide synthase (nNOS) in the adventitia of cerebral vessels. It dilates the arteries in response to shear stress, metabolic demands, pterygopalatine ganglion stimulation and chemoregulation. Subarachnoid hemorrhage (SAH) interrupts this regulation of cerebral blood flow. Hemoglobin, gradually released from erythrocytes in the subarachnoid space, destroys nNOS-containing neurons in the conductive arteries. This deprives the arteries of NO, leading to initiation of delayed vasospasm. But such vessel narrowing increases shear stress, which stimulates eNOS. This mechanism normally would lead to increased production of NO and dilation of arteries. However, a transient eNOS dysfunction evoked by an increase in the endogenous competitive NOS inhibitor, asymmetric dimethylarginine (ADMA), prevents this vasodilation. eNOS dysfunction has been recently shown to be evoked by increased levels of ADMA in cerebrospinal fluid (CSF) in response to the presence of bilirubin-oxidized fragments (BOXes). A direct cause of the increased ADMA CSF level is most likely decreased ADMA elimination owing to disappearance of ADMA-hydrolyzing enzyme [dimethylarginine dimethylaminohydrolase II (DDAH II)] immunoreactivity in the arteries in spasm. This eNOS dysfunction sustains vasospasm. CSF ADMA levels are closely associated with the degree and time course of vasospasm; when CSF ADMA levels decrease, vasospasm resolves. Thus, exogenous delivery of NO, inhibiting the L-arginine-methylating enzyme or stimulating DDAH II, may provide new therapeutic modalities to prevent and treat vasospasm. This paper will present results of pre-clinical studies supporting the NO-based hypothesis of delayed cerebral vasospasm development and its prevention by increased NO availability.

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Section: No and Pathomechanism(s) Of Delayed Cerebral Vasospasmsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Dysfunction of nitric oxide synthases as a cause and therapeutic target in delayed cerebral vasospasm after SAH

Pluta

2006

Neurological Research

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“…Nitrite has recently shown promise as a pharmacological agent in several models (16,17). It has been demonstrated that exogenous nitrite may exert cytoprotective effects in I/R injury (11,16).…”

Section: Discussionmentioning

confidence: 99%

“…A cytoprotective role for low pharmacological doses of nitrite in the setting of myocardial, liver, kidney, and brain ischemiareperfusion (I/R) injury has recently been demonstrated independently by a number of research groups (11,(16)(17)(18). The exact mechanisms behind the cytoprotective effects of exogenous nitrite, however, are still a matter of debate.…”

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confidence: 99%

Nitrite reductase activity of myoglobin regulates respiration and cellular viability in myocardial ischemia-reperfusion injury

Hendgen‐Cotta

Merx

Shiva

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

373

353

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The nitrite anion is reduced to nitric oxide (NO • ) as oxygen tension decreases. Whereas this pathway modulates hypoxic NO • signaling and mitochondrial respiration and limits myocardial infarction in mammalian species, the pathways to nitrite bioactivation remain uncertain. Studies suggest that hemoglobin and myoglobin may subserve a fundamental physiological function as hypoxia dependent nitrite reductases. Using myoglobin wild-type ( +/+ ) and knockout ( −/− ) mice, we here test the central role of myoglobin as a functional nitrite reductase that regulates hypoxic NO • generation, controls cellular respiration, and therefore confirms a cytoprotective response to cardiac ischemia-reperfusion (I/R) injury. We find that myoglobin is responsible for nitrite-dependent NO • generation and cardiomyocyte protein iron-nitrosylation. Nitrite reduction to NO • by myoglobin dynamically inhibits cellular respiration and limits reactive oxygen species generation and mitochondrial enzyme oxidative inactivation after I/R injury. In isolated myoglobin +/+ but not in myoglobin −/− hearts, nitrite treatment resulted in an improved recovery of postischemic left ventricular developed pressure of 29%. In vivo administration of nitrite reduced myocardial infarction by 61% in myoglobin +/+ mice, whereas in myoglobin −/− mice nitrite had no protective effects. These data support an emerging paradigm that myoglobin and the heme globin family subserve a critical function as an intrinsic nitrite reductase that regulates responses to cellular hypoxia and reoxygenation. myoglobin knockout mice

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“…11 In humans, dietary nitrate and nitrite sources have been demonstrated to lower blood pressure [12][13][14] and decrease oxygen consumption during submaximal and maximal aerobic exercise. 15,16 In animal models, nitrite has been demonstrated to enhance mucosal blood flow and serve antimicrobial functions, 17 protect against heart attack 18 and stroke, 19 and reverse vascular inflammation from a high fat diet. 20 Gastroprotective and blood pressure-lowering effects of dietary nitrate are abolished by frequent spitting after nitrate consumption or by antiseptic mouthwash.…”

Section: Introductionmentioning

confidence: 99%

Nitrate and Nitrite Content of Human, Formula, Bovine, and Soy Milks: Implications for Dietary Nitrite and Nitrate Recommendations

Hord

Ghannam

Garg

et al. 2011

Breastfeeding Medicine

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Background: Estimation of nitrate and nitrite concentrations of milk sources may provide insight into potential health risks and benefits of these food sources for infants, children, and adults. The World Health Organization and American Academy of Pediatrics recommends exclusive consumption of human milk for the first 6 months of life. Human milk is known to confer significant nutritional and immunological benefits for the infant. Consumption of formula, cow's, and soy milk may be used as alternatives to human milk for infants. Methods: We sought to estimate potential exposure to nitrate and nitrite in human, formula, bovine, and soy milk to inform total dietary exposure estimates and recommendations. Using sensitive quantitative methodologies, nitrite and nitrate were analyzed in different samples of milk. Results: Human milk concentrations of colostrum (expressed days 1-3 postpartum; n ¼ 12), transition milk (expressed days 3-7 postpartum; n ¼ 17), and mature milk (expressed >7 days postpartum; n ¼ 50) were 0.08 mg/100 mL nitrite and 0.19 mg/100 mL nitrate, 0.001 mg/100 mL nitrite and 0.52 mg/100 mL nitrate, and 0.001 mg/100 mL nitrite and 0.3 mg/100 mL nitrate, respectively, revealing that the absolute amounts of these anions change as the composition of milk changes. When expressed as a percentage of the World Health Organization's Acceptable Daily Intake limits, Silk Ò Soy Vanilla (WhiteWave Foods, Broomfield, CO) intake could result in high nitrate intakes (104% of this standard), while intake of Bright Beginnings Soy Pediatric

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Nitrite Infusions to Prevent Delayed Cerebral Vasospasm in a Primate Model of Subarachnoid Hemorrhage

Cited by 247 publications

References 82 publications

Dysfunction of nitric oxide synthases as a cause and therapeutic target in delayed cerebral vasospasm after SAH

Dysfunction of nitric oxide synthases as a cause and therapeutic target in delayed cerebral vasospasm after SAH

Nitrite reductase activity of myoglobin regulates respiration and cellular viability in myocardial ischemia-reperfusion injury

Nitrate and Nitrite Content of Human, Formula, Bovine, and Soy Milks: Implications for Dietary Nitrite and Nitrate Recommendations

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