Phosphoramidon prevents cerebral vasospasm following subarachnoid hemorrhage in dogs: The relationship to endothelin-1 levels in the cerebrospinal fluid

Matsumura, Yasuo; Ikegawa, Ruriko; Suzuki, Yasunori; Takaoka, Masanori; Uchida, Takeshi; Kido, Hiroyuki; Shinyama, Hiroshi; Hayashi, Kazutaka; Watanabe, Masahiro; Morimoto, Shiro

doi:10.1016/0024-3205(91)90249-b

Cited by 128 publications

(43 citation statements)

References 24 publications

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“…This peptide possesses a wide variety of biological actions (Rubanyi & Botelho, 1991) and may play a role in the various cardiovascular disorders such as cerebral vasospasm after subarachnoid haemorrhage (Matsumura et al, 1991), acute renal failure (Kon & Badr 1991), heart failure (Margulies et al, 1990), atherosclerosis (Lerman et al, 1991) and hypertension (Vanhoutte, 1993;Liischer et al, 1993). Circulating ET-1 concentrations are increased during hypertension (Kohno et al, 1991;Widimsky et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Role of endothelin‐1 and the ET_A receptor in the maintenance of deoxycorticosterone acetate‐salt‐induced hypertension

Fujita

Matsumura

Kita

et al. 1995

British J Pharmacology

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The intravenous bolus injection of FR139317 (10mgkg-') produced a slight decrease in blood pressure in the control rats and in the DOCA-salt hypertensive rat, FR139317 had a more pronounced hypotensive effect. 6 We propose that ET-1 production in vascular tissues is increased in DOCA-salt hypertensive rats. In addition, our study indicates the pathophysiological importance of increased endogenous ET-1 in the maintenance of DOCA-salt-induced hypertension, through interaction of the peptide with ETA receptors.

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Section: Introductionmentioning

confidence: 99%

Role of endothelin‐1 and the ET_A receptor in the maintenance of deoxycorticosterone acetate‐salt‐induced hypertension

Fujita

Matsumura

Kita

et al. 1995

British J Pharmacology

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“…[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. [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.…”

Section: Discussionmentioning

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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“…Thus, a specific inhibitor of ECE may have beneficial effects in the prevention and/or treatment of certain diseases. Most recently, we found that intracisternal administration of phosphoramidon effectively suppressed the development of cerebral vasespasm tbllowing subarachnoid hemorrhage in the canine 'two-hemorrhage' model and suggested that ET-1 may be a causal factor in the cerebral vasospasm [33]. The pathophysiological significance of ET-3 remains the subject of ongoing studies.…”

Section: As Described [35] Cultured Ecs Release Et-i In a Time-depementioning

confidence: 96%

Phosphoramidon‐sensitive endothelin‐converting enzyme in vascular endothelial cells converts big endothelin‐1 and big endothelin‐3 to their mature form

et al. 1992

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Incubation of big endothelin‐3 (big ET‐31–41) with the membrane fraction obtained from cultured endothelial cells (ECs) resulted in an increase in immunoreactive‐ET (IR‐ET). This increasing activity was markedly suppressed by phosphoramidon, which is known to inhibit the conversion of big ET‐11–39 to ET‐11–21. Reverse‐phase HPLC of the incubation mixture of the membrane fraction with big ET‐3 revealed one major IR‐ET component corresponding to the elution position of synthetic ET‐31–21. When the cultured ECs were incubated with big ET‐3, a conversion to the mature ET‐3, as well as an endogenous ET‐1 generation, was observed. Both responses were markedly suppressed by phosphoramidon. By the gel filtration of 0.5% CHAPS‐solubilized fraction of membrane pellets or ECs, the molecular mass of the proteinase which converts big ET‐1 and big ET‐3 to their mature form was estimated to be 300–350 kDa. Phosphoramidon almost completely abolished both converting activities of the proteinase. We conclude that the above type of phosphoramidon‐sensitive metalloproteinase functions as an ET‐converting enzyme to generate the mature form from big ET‐1 and big ET‐3 in ECs.

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Phosphoramidon prevents cerebral vasospasm following subarachnoid hemorrhage in dogs: The relationship to endothelin-1 levels in the cerebrospinal fluid

Cited by 128 publications

References 24 publications

Role of endothelin‐1 and the ET_A receptor in the maintenance of deoxycorticosterone acetate‐salt‐induced hypertension

Role of endothelin‐1 and the ET_A receptor in the maintenance of deoxycorticosterone acetate‐salt‐induced hypertension

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

Phosphoramidon‐sensitive endothelin‐converting enzyme in vascular endothelial cells converts big endothelin‐1 and big endothelin‐3 to their mature form

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Phosphoramidon prevents cerebral vasospasm following subarachnoid hemorrhage in dogs: The relationship to endothelin-1 levels in the cerebrospinal fluid

Cited by 128 publications

References 24 publications

Role of endothelin‐1 and the ETA receptor in the maintenance of deoxycorticosterone acetate‐salt‐induced hypertension

Role of endothelin‐1 and the ETA receptor in the maintenance of deoxycorticosterone acetate‐salt‐induced hypertension

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

Phosphoramidon‐sensitive endothelin‐converting enzyme in vascular endothelial cells converts big endothelin‐1 and big endothelin‐3 to their mature form

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Role of endothelin‐1 and the ET_A receptor in the maintenance of deoxycorticosterone acetate‐salt‐induced hypertension

Role of endothelin‐1 and the ET_A receptor in the maintenance of deoxycorticosterone acetate‐salt‐induced hypertension