Effect of intracarotid nitric oxide on primate cerebral vasospasm after subarachnoid hemorrhage

Afshar, John K. B.; Pluta, Ryszard; Boock, Robert J.; Thompson, B. Gregory; Oldfield, Edward H.

doi:10.3171/jns.1995.83.1.0118

Cited by 129 publications

(63 citation statements)

References 29 publications

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“…45,46 Involvement of NO has been implicated in SAH. 6,21,47,48 Several investigators have shown that production of cGMP in vascular smooth muscle is decreased following SAH. 16,17 However, since NO donors can still produce relaxation of these blood vessels, 49 decreased vasodilatation may be due to reduction in basal cerebral NO levels.…”

Section: Discussionmentioning

confidence: 99%

Effects of S -Nitrosoglutathione on Acute Vasoconstriction and Glutamate Release After Subarachnoid Hemorrhage

Sehba

Ding

Chereshnev

et al. 1999

Stroke

101

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Background and Purpose-Subarachnoid hemorrhage (SAH) causes acute vasoconstriction that contributes to ischemic brain injury shortly after the initial bleed. It has been theorized that decreased availability of nitric oxide (NO) may contribute to acute vasoconstriction. Therefore we examined the effect of the NO donor N-nitroso glutathione (GSNO) on acute vasoconstriction and early ischemic glutamate release after experimental SAH. Methods-SAH was induced by the endovascular suture method in anesthetized rats. GSNO (1 mol/L/kg, nϭ31) or saline (nϭ21) was injected 5 minutes after SAH. Sham-operated rats received GSNO (1 mol/L/kg, nϭ5) 5 minutes after sham surgery. Arterial and intracranial pressures, cerebral blood flow (CBF), and extracellular glutamate release were measured serially for 60 minutes after SAH. SAH size was determined, and vascular measurements were made histologically. Results-GSNO had no effect on resting blood pressure, intracranial pressure, cerebral perfusion pressure, or CBF in sham-operated animals. However, administration of GSNO after SAH was associated with significantly increased CBF (161.6Ϯ26.6% versus saline 37. Key Words: cerebral blood flow Ⅲ glutamates Ⅲ nitric oxide Ⅲ subarachnoid hemorrhage Ⅲ vasoconstriction C erebral arteries respond to subarachnoid hemorrhage (SAH) with a biphasic contraction that begins minutes after the bleed and delayed vasospasm more than 48 hours later. 1-3 Although a great deal is known about the mechanisms and management of delayed vasospasm, less is known about the physiology, treatment, and importance of acute vasoconstriction. Different mechanisms may underlie the 2 processes, 4 and a great variety have been implicated. [5][6][7][8][9][10][11] Recently we have shown that acute vasoconstriction is associated with decreased cerebral blood flow (CBF), ischemic glutamate release, and premature mortality after experimental SAH. 12 If acute vasoconstriction could be pharmacologically attenuated, then SAH-induced brain injury could potentially be reduced.Resting cerebrovascular tone is maintained by a balance between opposing vasoconstrictive and vasodilatory forces, and both are pathologically altered in the acute phases of SAH. One of the most important of these is the resting vasodilatory influence of nitric oxide (NO). NO has been shown to induce endothelium-dependent vasodilatation via a cGMP-mediated See Editorial Comment, page 1961 mechanism. 13 Loss of endothelium-mediated vasodilatation 14,15 and decreased cGMP production 16,17 have been shown to contribute to vasospasm after SAH.Because administration of an NO donor after SAH should potentially restore c-GMP-dependent vasodilatation, a number of different NO donors have been tested for their ability to attenuate delayed vasospasm. 18 -21 Recent studies have suggested that sodium nitroprusside administered intrathecally 22 or intra-arterially 23 increases CBF acutely after SAH. In preliminary studies we have found that it also causes profound hypotension in this setting (J.B. Bederson, MD, et al, ...

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Section: Discussionmentioning

confidence: 99%

Effects of S -Nitrosoglutathione on Acute Vasoconstriction and Glutamate Release After Subarachnoid Hemorrhage

Sehba

Ding

Chereshnev

et al. 1999

Stroke

101

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“…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 .…”

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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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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“…Recently, it was reported that nitric oxide (NO), [20,22,50] a potent vasodilator, [20,22,42] is directly involved in the regulation of CBF. Moreover, a reversal of vasospasm by direct intracarotid infusion of NO solution [1] indicates that there may be decreased availability of NO at the time of vasospasm. The combination of the continuous presence of low levels of ET-1 in the perivascular space, such as those observed in our experiments, with decreased NO production due to the concomitant disappearance of NO synthase activity from the adventitia of the vessel [43] or a decrease in NO availability due to a "sink effect" of hemoglobin, [18,22] could be responsible for vasospasm.…”

Section: Vasospasm and Et-1mentioning

confidence: 99%

“…The combination of the continuous presence of low levels of ET-1 in the perivascular space, such as those observed in our experiments, with decreased NO production due to the concomitant disappearance of NO synthase activity from the adventitia of the vessel [43] or a decrease in NO availability due to a "sink effect" of hemoglobin, [18,22] could be responsible for vasospasm. Because a decrease in NO availability results in increased ET-1 production, [28,37] the decrease of vasospasm in response to ET-1 receptor antagonists [8,23,34,38,57] as well as to NO [1] may occur because both approaches tend to recover the normal balance between ET-1 and NO.…”

Section: Vasospasm and Et-1mentioning

confidence: 99%

Source and cause of endothelin-1 release to cerebrospinal fluid after subarachnoid hemorrhage

Pagnanelli

Barrer²

1997

FOC

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Despite years of research, delayed cerebral vasospasm remains a serious complication of subarachnoid hemorrhage (SAH). Recently, it has been proposed that endothelin-1 (ET-1) mediates vasospasm. The authors examined this hypothesis in a series of experiments. In a primate model of SAH, serial ET-1 levels were measured in samples from the perivascular space by using a microdialysis technique and in cerebrospinal fluid (CSF) and plasma during the development and resolution of delayed vasospasm. To determine whether elevated ET-1 production was a direct cause of vasospasm or acted secondary to ischemia, the authors also measured ET-1 levels in plasma and CSF after transient cerebral ischemia. To elucidate the source of ET-1, they measured its production in cultures of endothelial cells and astrocytes exposed to oxyhemoglobin (10 μM), methemoglobin (10 μM), or hypoxia (11% oxygen). There was no correlation between the perivascular levels of ET-1 and the development of vasospasm or its resolution. Cerebrospinal fluid and plasma levels of ET-1 were not affected by vasospasm (CSF ET-1 levels were 9.3 ± 2.2 pg/ml and ET-1 plasma levels were 1.2 ± 0.6 pg/ml) before SAH and remained unchanged when vasospasm developed (7.1 ± 1.7 pg/ml in CSF and 2.7 ± 1.5 pg/ml in plasma). Transient cerebral ischemia evoked an increase of ET-1 levels in CSF (1 ± 0.4 pg/ml at the occlusion vs. 3.1 ± 0.6 pg/ml 4 hours after reperfusion; p < 0.05), which returned to normal (0.7 ± 0.3 pg/ml) after 24 hours. Endothelial cells and astrocytes in culture showed inhibition of ET-1 production 6 hours after exposure to hemoglobins. Hypoxia inhibited ET-1 release by endothelial cells at 24 hours (6.4 ± 0.8 pg/ml vs. 0.1 ± 0.1 pg/ml, control vs. hypoxic endothelial cells; p < 0.05) and at 48 hours (6.4 ± 0.6 pg/ml vs. 0 ± 0.1 pg/ml, control vs. hypoxic endothelial cells; p < 0.05), but in astrocytes hypoxia induced an increase of ET-1 at 6 hours (1.5 ± 0.6 vs. 6.4 ± 1.1 pg/ml, control vs. hypoxic astrocytes; p < 0.05). Endothelin-1 is released from astrocytes, but not endothelial cells, during hypoxia and is released from the brain after transient ischemia. There is no relationship between ET-1 and vasospasm in vivo or between ET-1 and oxyhemoglobin, a putative agent of vasospasm, in vitro. The increase in ET-1 levels in CSF after SAH from a ruptured intracranial aneurysm appears to be the result of cerebral ischemia rather than reflecting the cause of cerebral vasospasm.

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Effect of intracarotid nitric oxide on primate cerebral vasospasm after subarachnoid hemorrhage

Cited by 129 publications

References 29 publications

Effects of S -Nitrosoglutathione on Acute Vasoconstriction and Glutamate Release After Subarachnoid Hemorrhage

Effects of S -Nitrosoglutathione on Acute Vasoconstriction and Glutamate Release After Subarachnoid Hemorrhage

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

Source and cause of endothelin-1 release to cerebrospinal fluid after subarachnoid hemorrhage

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