Oxyhaemoglobin increases the production of endothelin-1 by endothelial cells in culture

Cocks, T. M.; Malta, Errol; King, Sontoria D.; Woods, Robyn L.; Angus, James A.

doi:10.1016/0014-2999(91)90425-p

Cited by 64 publications

(25 citation statements)

References 23 publications

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“…[9,24,40] On the contrary, we found that production of ET-1 by the cells was inhibited by exposure to oxyhemoglobin or methemoglobin. The discrepancy between our results and those of others [9,24,40] may be related to their use of a commercially available bovine double-crystallized hemoglobin (Sigma Chemical Co., St. Louis, MO), which is contaminated with hemin [27] and endotoxins [35] and which may be responsible for the increased production of ET-1 by the cells.…”

Section: Vasospasm and Et-1contrasting

confidence: 61%

“…[9,11,14,19,24,33,37,40,[47][48][49] This controversial [5,19] hypothesis is supported by a delayed onset of long-lasting spasm of the intracranial vessels produced by intracisternal administration of ET-1, [3,47] by an increase in ET-1 levels in CSF after SAH in humans, [11,14,48,49] and by a decrease in the incidence of vasospasm after use of ET-1 receptor antagonists. [8,23,34,38,57] Astrocytes, neurons, and pituitary cells produce ET-1.…”

Section: Discussionmentioning

confidence: 99%

“…[8,23,34,38,57] Astrocytes, neurons, and pituitary cells produce ET-1. [10,17,26,29,56] However, ET-1 is also released by endothelial and smooth-muscle cells when they are stimulated by oxyhemoglobin [9,24,40] and by astrocytes when they are stimulated by thrombin. [10] Thus, both the source and the mechanism of ET-1 presence in the subarachnoid space after SAH appear to be unclear.…”

Section: Discussionmentioning

confidence: 99%

“…[31,46] One of the potential oxyhemoglobin-related mechanisms of vasospasm is the release of endothelin-1 (ET-1), [3,33,37] a potent endothelium-derived vasoconstricting agent, [21,55] into the cerebrospinal fluid (CSF) after SAH. [3,11,14,15,19,21,25,33,[47][48][49] Not only are astrocytes, neurons, and pituitary cells a normal source of extraluminal ET-1, [10,17,26,29,56] but endothelial [9,24,40] and smooth-muscle [24] cells also release ET-1 when stimulated by oxyhemoglobin [9,24,40] or thrombin. [10 ] Because an increase in the levels of ET-1 in CSF has been described in patients with cerebral vasospasm and delayed ischemic neurological deficits after SAH, [11,14,48,49] the production of ET-1 may also be induced by ischemia.…”

mentioning

confidence: 99%

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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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Section: Vasospasm and Et-1contrasting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Pagnanelli

Barrer²

1997

FOC

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“…Other studies failed to demonstrate increased ET-1 release after extended incubation (3-24 hours) with NOS inhibitor 27,35,[38][39][40][41] (Figure). Importantly, the general inability of NOS inhibitor to increase ET-1 release does not seem to be because of the failure of NOS inhibitor to decrease NO because NOS inhibitor for 8 hours decreased basal NO by 75% but did not increase ET-1 release 41 (Figure; Figure S1).…”

Section: Endothelium: Staticmentioning

confidence: 93%

Nitric Oxide Inhibition of Endothelin-1 Release in the Vasculature

Rapoport

2014

Hypertension

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A key function of endothelial derived nitric oxide (NO) is to limit the constrictor capacity of endothelin (ET)-1.1,2 Thus, an imbalance between NO and ET-1 can result in ET-1-dependent increased vascular tone.1 Indeed, the importance of sustained, NO inhibition of the ET-1 drive to increase tone is exemplified in vivo by the rapid, ET-1-mediated arterial pressure elevation after acute NO synthase (NOS) inhibition. Moreover, the ET-1 pressor effect after NOS inhibition is independent of other pressor systems and, thus, reflects the relative importance of NO suppression of this ET-1 drive.2 Two, nonmutually exclusive mechanisms thought to underlie the ET-1 dependency of the increased vascular tone responsible for the NOS inhibitor-induced pressure elevation are (1) NO inhibition of constriction to endogenously released ET-1.1,2 This mechanism is essentially supported by demonstrations that NOS inhibitor enhanced the constrictor effects of exogenous ET-1 in several in vivo and ex vivo preparations. 3-14Thus, an assumption underlying these observations is that the constrictor actions of exogenous and endogenous ET-1 are similarly affected by NO; (2) NO inhibition of ET-1 release. 1,2Although the detailed mechanism underlying the NO inhibition of acute ET-1 release has not been clearly established, possibilities include decreased conversion of the immediate precursor to ET-1, big ET-1, to ET-1 15 and inhibition of pathways involved in the exocytosis of Weibel-Palade bodies, 16 endothelial granules that store ET-1. 17 However, it should be noted that in vivo findings that actually demonstrate the fundamental phenomenon of NO inhibition of ET-1 release are generally lacking.2 Thus, studies purported to demonstrate NO inhibition of ET-1 release have relied largely on isolated vessels and cultured endothelium, as described herein.This review assessed these in vitro findings, with a specific focus toward elucidating the mechanism underlying the NO-mediated negative regulation of ET-1-dependent increased arterial pressure, as demonstrated after acute NOS inhibitor in vivo.2 Findings referred to are mainly those of ET-1 release rather than contractility (eg, those in which ET receptor antagonist prevented the NOS inhibitor-induced decreased flow/increased pressure/tension). 12,18-25 The rationale for this emphasis is that findings based on contractility could reflect NOS inhibitor enhancement of ET-1 constriction rather than increased ET-1 release. Furthermore, we also focus on whether laminar shear stress influences the manifestation of NO inhibition of ET-1 release. That is, the endothelium of arteries that are anatomically linear is subjected to high levels of shear stress while, for example, at bifurcated arterial locations is subjected to low levels of shear stress, regions associated with atherosclerosis. 26 Acute NOS Inhibition/No Donors and ET-1 Release ArteriesIn rat heart perfused at constant flow, increased amounts of ET-1 were detected in the coronary effluent of samples collected for the final 5 to 15 minutes ...

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Hemoglobin Increases Endothelin-1 in Endothelial Cells by Decreasing Nitric Oxide

Lin

Macdonald

Marton

et al. 2001

Biochemical and Biophysical Research Communications

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Oxyhaemoglobin increases the production of endothelin-1 by endothelial cells in culture

Cited by 64 publications

References 23 publications

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

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

Nitric Oxide Inhibition of Endothelin-1 Release in the Vasculature

Hemoglobin Increases Endothelin-1 in Endothelial Cells by Decreasing Nitric Oxide

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