Endothelin, vasoconstriction, and endothelial damage in Raynaud's phenomenon

Cimminiello, Claudio; Milani, Massimo; Uberti, T.; Arpaia, Guido; Perolini, S.; Bonfardeci, Giuseppe

doi:10.1016/0140-6736(91)90772-h

Cited by 22 publications

(8 citation statements)

References 3 publications

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“…This is thermoneutral, well below the thermal sweating threshold, but warm enough not to trigger vasospasm in the patients. The finding that ET-1 levels did not differ at baseline is contrary to earlier reports, which described higher baseline ET-1 concentrations in seven patients with primary RP relative to controls13 and mildly raised baseline levels in 15 patients compared with controls 14. The present findings concur with the baseline studies of Smits et al , who studied a mixed group of 10 patients with primary and scleroderma associated RP 15…”

Section: Discussionsupporting

confidence: 73%

Digital vascular responses and serum endothelin-1 concentrations in primary and secondary Raynaud's phenomenon

Smyth

Bell²,

Bruce³

et al. 2000

Annals of the Rheumatic Diseases

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Objective-To determine circulating endothelin-1 levels (ET-1) in patients with primary or secondary associated Raynaud's phenomenon (RP) under resting conditions and in response to cold provocation. Methods-Patients were categorised as primary RP (18) or scleroderma associated RP (14). Finger blood flow was measured by venous occlusion plethysmography at finger temperatures of 32°C and 24°C. Vasospasm was detected as a finger systolic pressure of 0 mm Hg after standardised provocative cooling. Severity of vasospasm was assessed by the level of cooling required to provoke spasm. Plasma ET-1 levels were measured in antecubital blood withdrawn under baseline conditions (finger 32°C) and at the point of vasospasm. Measurements were also made in 19 matched control subjects. Results-Finger blood flow was lower in patients with RP than in controls, with no diVerence between the two RP groups. Vasospasm occurred in all patients with RP but not in any control subjects and a grading system of severity was established. Baseline plasma ET-1 levels were similar in patients with RP and controls. Increases in ET-1 levels at the point of vasospasm in patients or corresponding timepoint in controls were also similar. There was no significant diVerence between the ET-1 levels in the two RP subgroups when the fingers were warm or when vasospasm was present. Conclusions-These results do not support the hypothesis that ET-1 plays a part in the pathogenesis of RP. Objective testing is a useful adjunct to the clinical diagnosis of RP and allows assignment of a severity grade.

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Section: Discussionsupporting

confidence: 73%

Digital vascular responses and serum endothelin-1 concentrations in primary and secondary Raynaud's phenomenon

Smyth

Bell²,

Bruce³

et al. 2000

Annals of the Rheumatic Diseases

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“…The hypothesis that an imbalance in the control of vascular endothelial responses, in favour of vasoconstriction, might underlie the increased vasospasm has led to investigation of a number of different endothelium‐dependent responses in Raynaud's. The endothelium‐dependent vasocontrictor endothelin‐1 (ET‐1) is increased with cold exposure [8, 9], and a number of investigators have identified increased levels of ET‐1 in subjects with PRP [10‐13] but without identifying a consistent rise with cold challenge. On the other side of the balance, reduced levels of endothelium‐dependent vasodilators have been found, including bradykinin [14], in response to acetylcholine both in the finger microcirculation [5] and brachial artery [6], but not by all groups [15–17], and not consistently.…”

Section: Introductionmentioning

confidence: 99%

Seasonal differences in finger skin temperature and microvascular blood flow in healthy men and women are exaggerated in women with primary Raynaud's phenomenon

Macdonald²,

Jy³

et al. 2001

Brit J Clinical Pharma

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Aims Patients with primary Raynaud's phenomenon (PRP) have more severe symptoms in the winter. The aetiology of this is more complex than simply increased vasoconstriction in response to the immediate ambient temperature. The aim of this study was to investigate differences in skin temperature (Tsk), microvascular blood ow and responses to endothelium-dependent and independent vasodilators in healthy controls, and women with PRP under identical environmental temperatures but in different seasons. Methods Ten women with PRP were compared with age matched women (10) and men (10). Finger skin responses were recorded immediately on arrival, after stabilizing in a temperature regulated laboratory at 22±24u C, and at matched warm (35u C) and cold (15u C) Tsk in the winter and summer. Baseline red blood cell¯ux (r.b.c.¯ux), and the change in¯ux in response to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) were recorded by laser Doppler¯uxmetry at the warm and cold Tsk. Results Arrival Tsk were signi®cantly cooler for all subjects during the winter (mean seasonal difference x2.6u C, P<0.0001), and markedly colder in subjects with PRP (mean seasonal difference x3.5u C, P<0.0005). Statistically signi®cant seasonal differences persisted in all subjects at stable Tsk despite an identical laboratory temperature (mean difference 1.3u C, P<0.0001). To achieve comparable controlled ®nger Tsk a signi®cantly colder local environment was required for male controls (mean of x2.1u C, P<0.0001), and a signi®cantly warmer environment for subjects with PRP (mean of + 2.4u C, P<0.0001) compared with female controls. This needed to be warmer in the winter, by a mean of 2.4u C, than the summer for all subjects. Vasodilatation in response to ACh, but not SNP, was signi®cantly smaller (P<0.0001) in the PRP group compared with the female controls for all visits, with most of this difference arising in the winter visits (P<0.01). Conclusions There is a seasonal and persistent in¯uence on ®nger Tsk, and microvascular blood¯ow in healthy men and women, which modi®es the observed responses to immediate changes in ®nger Tsk. The seasonal differences are greater in women than men, and are further exaggerated in women with PRP, in whom this is associated with reduced endothelium-dependent vasodilatation.

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“…Although there are some reports on the coagulation and fibrinolysis system in patients with Raynaud's phe nomenon, most of the subjects studied have had PSS [5][6][7][8][9][10][11]. Furthermore, to our knowledge there has been no report concerning plasma thrombomodulin levels (TM) in patients with this phenomenon.…”

Section: Sle Patients Nsmentioning

confidence: 80%

“…However, Cimminiello et al [11] have reported that plasma levels of ET and vWF in patients with Raynaud's phenomenon were significantly raised, but they could not find any changes in ET and vWF levels after exposure of the hand to cold water. Smith et al [19] also found no sig nificant differences of plasma ET levels between patients with and those without Raynaud's phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Effect of Total-Body Cold Exposure on Plasma Concentrations of von Willebrand Factor, Endothelin-1 and Thrombomodulin in Systemic Lupus erythematosus Patients with or without Raynaud’s Phenomenon

et al. 1992

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The effect of total-body cold exposure on plasma concentrations of von Willebrand factor (vWF), endothelin-1 (ET) and thrombomodulin (TM), all of which are considered to be generated from the endothelium, was studied in systemic lupus erythematosus (SLE) patients with and without Raynaud’s phenomenon. The plasma levels of vWF, ET and TM in SLE patients, irrespective of the presence of Raynaud’s phenomenon, were significantly higher than in normal controls even before the cold provocation test. After the cold provocation test, plasma levels of vWF and ET were significantly higher in SLE patients with Raynaud’s phenomenon than in those without and in normal controls. No significant increase in TM was observed in either the SLE patients or the controls. These results suggest that SLE patients, regardless of the presence of Raynaud’s phenomenon, are in a hypercoagulable state and that this state may be further intensified by cold exposure. Hence, it is concluded that we should consider antithrombotic therapy for SLE patients, especially those with Raynaud’s phenomenon, to prevent unwanted activation of the coagulation system and possible endothelial damage.

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Endothelin, vasoconstriction, and endothelial damage in Raynaud's phenomenon

Cited by 22 publications

References 3 publications

Digital vascular responses and serum endothelin-1 concentrations in primary and secondary Raynaud's phenomenon

Digital vascular responses and serum endothelin-1 concentrations in primary and secondary Raynaud's phenomenon

Seasonal differences in finger skin temperature and microvascular blood flow in healthy men and women are exaggerated in women with primary Raynaud's phenomenon

Effect of Total-Body Cold Exposure on Plasma Concentrations of von Willebrand Factor, Endothelin-1 and Thrombomodulin in Systemic Lupus erythematosus Patients with or without Raynaud’s Phenomenon

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