Raynaud's phenomenon

Dowd, P.M.; Goldsmith, P. C.; Bull, HelenA.; Burnstock, Geoffrey; Foreman, J. C.; Marshall, Ian

doi:10.1016/s0140-6736(95)92169-9

Cited by 40 publications

(18 citation statements)

References 32 publications

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“…Diminished sympathetic nerve activity also occurs. Raynaud's phenomenon, in which there is inappropriate constriction of blood vessels to the digits on exposure to cold, is often an early event in the development of systemic sclerosis (93). There is early functional deficit of the vascular endothelium, but ANS dysfunction has also been linked with systemic sclerosis.…”

Section: Pathophysiology Of Autonomic Neurotransmissionmentioning

confidence: 99%

Autonomic Neurotransmission: 60 Years Since Sir Henry Dale

Burnstock

2009

Annu. Rev. Pharmacol. Toxicol.

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109

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In the early twentieth century, Sir Henry Dale and others described brilliant studies of autonomic neurotransmission utilizing acetylcholine and noradrenaline. However, within the past 60 years, new discoveries have changed our understanding of the organization of the autonomic nervous system, including the structure and function of the nonsynaptic autonomic neuroeffector junction, the multiplicity of neurotransmitters, cotransmission, neuromodulation, dual control of vascular tone by perivascular nerves and endothelial cells, the molecular biology of receptors, and trophic signaling. Further, it is now recognized that an outstanding feature of autonomic neurotransmission is the inherent plasticity afforded by its structural and neurochemical organization and the interaction between expression of neural mediators and environmental factors. In this way, autonomic neurotransmission is matched to ongoing changes in demands and can sometimes be compensatory in pathophysiological situations.

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Section: Pathophysiology Of Autonomic Neurotransmissionmentioning

confidence: 99%

Autonomic Neurotransmission: 60 Years Since Sir Henry Dale

Burnstock

2009

Annu. Rev. Pharmacol. Toxicol.

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109

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“…When it occurs in isolation, it is designated primary Raynaud's phenomenon (RP) to distinguish it from those cases in which there is an underlying or associated pathology. It affects ϳ10% of the adult population, with a predilection for females, and up to 5% of patients presenting with this condition later develop an autoimmune rheumatic disorder, such as systemic sclerosis (SSc; scleroderma) (2). Successful treatment is often difficult, and although clinical trials suggest that vasodilators can be effective, the responses of individual patients to a particular agent are often idiosyncratic.…”

mentioning

confidence: 99%

Losartan therapy for Raynaud's phenomenon and scleroderma: Clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial

Dziadzio

Denton

Smith

et al. 1999

Arthritis & Rheumatism

277

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Objective. To compare the efficacy and tolerability of losartan, an antagonist of angiotensin II receptor type 1, with nifedipine for the treatment of primary and secondary Raynaud's phenomenon (RP) in a pilot study.Methods. In a randomized, parallel-group, controlled trial, patients with primary RP (n ‫؍‬ 25) or RP secondary to systemic sclerosis (SSc [scleroderma]; n ‫؍‬ 27) were allocated to receive 12 weeks' treatment with either losartan (50 mg/day) or nifedipine (40 mg/day). Primary outcome variables were the severity and frequency of RP episodes and findings on vascular measurements, including thermography and laser Doppler flowmetry. Serum levels of soluble adhesion molecules, endothelin 1, fibrinogen, von Willebrand factor, and procollagen type I N-terminal propeptide (PINP) were also measured.Results. There was a reduction in the severity of RP episodes following treatment with losartan and with nifedipine, but this effect was greater in the losartan arm of the study (P < 0.05): episode frequency was reduced only in the losartan group (P < 0.01 versus baseline). Symptomatic improvement was associated with a significant reduction in soluble vascular cell adhesion molecule 1 and PINP (P < 0.01). Subgroup analysis suggested that although these biochemical changes occurred mainly in SSc patients, the clinical benefit was greater in the primary RP group.Conclusion. This study confirms the tolerability of short-term treatment of RP with losartan, and our data suggest its clinical benefit. Further evaluation of this drug as a long-term treatment for SSc-associated RP should be considered, since it may have additional disease-modifying potential.Episodic digital ischemia provoked by cold and emotion was first described by Maurice Raynaud over 130 years ago (1). When it occurs in isolation, it is designated primary Raynaud's phenomenon (RP) to distinguish it from those cases in which there is an underlying or associated pathology. It affects ϳ10% of the adult population, with a predilection for females, and up to 5% of patients presenting with this condition later develop an autoimmune rheumatic disorder, such as systemic sclerosis (SSc; scleroderma) (2). Successful treatment is often difficult, and although clinical trials suggest that vasodilators can be effective, the responses of individual patients to a particular agent are often idiosyncratic.The pathogenesis of the vascular dysfunction underlying RP is incompletely understood, and relatively few well-controlled clinical trials with vasoactive drugs have been undertaken. Lack of distinction between primary and secondary RP in some of these studies makes their interpretation difficult. Calcium channel antagonists such as nifedipine have been shown to be effective (3-6), although striking differences in individual responses have been described (3,7). Moreover, efficacy is often particularly limited in patients with RP

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“…Alterations in a-or (3-adrenoceptors and increased sympathetic activity, which are frequently observed in patients with PRP and SSc [5][6][7], might constitute a plausible explanation. On the radial Radial Artcrv in Ravnaud's Phenomenon artery of normal subjects studied in vivo, a-receptors are present and sympathetic activation is able to produce active lumen constriction [22,23], However, this possibil ity does not fit in with the finding of a sustained reduction in lumen diameter in patients with PRP and SSc, the lack of modifications of systemic blood pressure and the direct measurement of normal sympathetic nerve activity pre viously observed in patients with PRP and SSc [24], Another possible interpretation is the presence of endo thelial dysfunction [6], Increased plasma levels of endothelin and a loss in calcitonin gene-related peptide con taining neurons have been previously reported in patients with PRP and SSc [25,26], Furthermore, the observation of a decreased ability to achieve a normal hand or finger blood How during body and head heating in RP [27] sug gests that the mechanism of flow dilation may be altered, the tendency for a decrease in blood flow causing a result ing decrease in diameter. An altered flow dilation mecha nism is a classical marker of endothelial dysfunction [27][28][29], This mechanism may be operating at the site of the radial artery for several reasons.…”

Section: Interpretation O F Resultsmentioning

confidence: 99%

“…Both in primary and secondary RP. an endothelial dysfunction has also been suggested [6,7], Whatever causes or theories pro posed, the final event leading to the clinical symptoms is the occlusion of the digital vessels.…”

mentioning

confidence: 99%

The Wall to Lumen Ratio of the Radial Artery in Patients with Raynaud’s Phenomenon

Mourad

Priollet²,

Girerd³

et al. 1997

J Vasc Res

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The pathophysiology of Raynaud’s phenomenon (RP) remains an enigma. Whatever theories proposed, the final event leading to the clinical symptoms is the occlusion of digital vessels. However, the possibility that the upstream large arterial vessels contribute to vasopasm has never been investigated. We used a high resolution echo-tracking device to calculate lumen diameter, wall thickness, and circumferential wall stress upstream the digital arteries, i.e. at the site of the radial artery. Fifteen control women, 15 age-matched women with primary RP (PRP) and 15 women presenting with a secondary RP due to systemic sclerosis (SSc) were included in the study. All vasodilating agents were discontinued 72 h before the study session, which was conducted in a room with a stable ambient temperature of 22°C Radial artery internal diameter, intima-media wall thickness, and mean arterial pressure were measured simultaneously. Internal diameter of patients with RP was significantly decreased (p& < 0.001 vs. controls) whereas intima-media wall thickness and mean arterial pressure were closely similar in the three groups, resulting in an increase in the wall to lumen ratio. Thus, circumferential wall stress was significantly smaller (p& < 0.05 vs. controls) in patients with RP. In conclusion, this study demonstrates that in patients with RP, wall to lumen ratio is increased and circumferential wall stress is reduced at the level of the radial artery. It is suggested that the geometrical and mechanical changes of this artery may favor the downstream occlusive phenomena observed in patients with PRP and SSc.

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Raynaud's phenomenon

Cited by 40 publications

References 32 publications

Autonomic Neurotransmission: 60 Years Since Sir Henry Dale

Autonomic Neurotransmission: 60 Years Since Sir Henry Dale

Losartan therapy for Raynaud's phenomenon and scleroderma: Clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial

The Wall to Lumen Ratio of the Radial Artery in Patients with Raynaud’s Phenomenon

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Raynaud's phenomenon

Cited by 40 publications

References 32 publications

Autonomic Neurotransmission: 60 Years Since Sir Henry Dale

Autonomic Neurotransmission: 60 Years Since Sir Henry Dale

Losartan therapy for Raynaud's phenomenon and scleroderma: Clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial

The Wall to Lumen Ratio of the Radial Artery in Patients with Raynaud&rsquo;s Phenomenon

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The Wall to Lumen Ratio of the Radial Artery in Patients with Raynaud’s Phenomenon