Neuronal regulators and vascular dysfunction in Raynaud's phenomenon and systemic sclerosis.

Raynaud's phenomenon (RP) results from an exaggerated cutaneous vasospastic response to cold or emotional stress. The mechanisms that lead to impaired cutaneous vascular tone are complex. The regulation of cutaneous vasoconstriction and vasodilation, involves altered sympathetic nerve activity and a host of neuronal regulators, including adrenergic and non-adrenergic, as well as REDOX signalling and other signalling such as the RhoA/ROCK pathway. This review summarises the literature concerning the regulation of vascular tone by neurohumoral factors that may be involved in RP and systemic sclerosis (SSc).

[1]  N. Flavahan.  Regulation of vascular reactivity in scleroderma: new insights into Raynaud's phenomenon. , 2008, Rheumatic diseases clinics of North America.

[2]  S. Flavahan,et al.  Estrogen increases smooth muscle expression of alpha2C-adrenoceptors and cold-induced constriction of cutaneous arteries. , 2007, American journal of physiology. Heart and circulatory physiology.

[3]  Herbert Herzog,et al.  NPY and receptors in immune and inflammatory diseases. , 2007, Current topics in medicinal chemistry.

[4]  Jason U Tilan,et al.  NPY and NPY receptors in vascular remodeling. , 2007, Current topics in medicinal chemistry.

[5]  J. Liao,et al.  Rho Kinase (ROCK) Inhibitors , 2007, Journal of cardiovascular pharmacology.

[6]  S. Archer,et al.  Oxygen Activates the Rho/Rho-Kinase Pathway and Induces RhoB and ROCK-1 Expression in Human and Rabbit Ductus Arteriosus by Increasing Mitochondria-Derived Reactive Oxygen Species: A Newly Recognized Mechanism for Sustaining Ductal Constriction , 2007, Circulation.

[7]  Lydia E. Kuo,et al.  Corrigendum to “Stress, NPY and vascular remodeling: Implications for stress-related diseases” [Peptides 28 (2007) 435–440] , 2007, Peptides.

[8]  N. Flavahan,et al.  Cold-induced cutaneous vasoconstriction is mediated by Rho kinase in vivo in human skin. , 2007, American journal of physiology. Heart and circulatory physiology.

[9]  Lydia E. Kuo,et al.  Stress, NPY and vascular remodeling: Implications for stress-related diseases , 2007, Peptides.

[10]  J. Liao,et al.  Rho GTPases, statins, and nitric oxide. , 2005, Circulation research.

[11]  Francesco Boin,et al.  Understanding, assessing and treating Raynaud's phenomenon , 2005, Current opinion in rheumatology.

[12]  J. Cooke,et al.  Mechanisms of Raynaud’s disease , 2005, Vascular medicine.

[13]  A. Herrick.  Pathogenesis of Raynaud's phenomenon. , 2005, Rheumatology.

[14]  J. Murabito,et al.  The incidence and natural history of Raynaud's phenomenon in the community. , 2005, Arthritis and rheumatism.

[15]  M. Matucci-Cerinic,et al.  Estrogens and neuropeptides in Raynaud's phenomenon. , 2005, Rheumatic diseases clinics of North America.

[16]  N. Tublitz,et al.  Mechanisms of vasoactive intestinal peptide-mediated vasodilation in human skin. , 2004, Journal of applied physiology.

[17]  John M. Johnson,et al.  Neuropeptide Y antagonism reduces reflex cutaneous vasoconstriction in humans. , 2004, American journal of physiology. Heart and circulatory physiology.

[18]  S. Brain,et al.  Vascular actions of calcitonin gene-related peptide and adrenomedullin. , 2004, Physiological reviews.

[19]  S. Flavahan,et al.  Rho Kinase Mediates Cold-Induced Constriction of Cutaneous Arteries: Role of &agr;2C-Adrenoceptor Translocation , 2004, Circulation research.

[20]  H. Struijker‐Boudier,et al.  Calcitonin gene–related peptide: Exploring its vasodilating mechanism of action in humans , 2003, Clinical pharmacology and therapeutics.

[21]  N. Flavahan,et al.  Cooling evokes redistribution of alpha2C-adrenoceptors from Golgi to plasma membrane in transfected human embryonic kidney 293 cells. , 2001, Molecular pharmacology.

[22]  Kozo Kaibuchi,et al.  Rho-family GTPases in cadherin-mediated cell — cell adhesion , 2001, Nature Reviews Molecular Cell Biology.

[23]  J. Block,et al.  Raynaud's phenomenon , 2001, The Lancet.

[24]  A. del Rosso,et al.  Nerve growth factor and neuropeptides circulating levels in systemic sclerosis (scleroderma) , 2001, Annals of the rheumatic diseases.

[25]  L. Angrisani,et al.  [Relationship among VIP plasma levels, esophageal dysfunction, and microcirculation in systemic sclerosis]. , 2000, Minerva medica.

[26]  R. Girgis,et al.  Effects of Menstrual Cycle and Race on Peripheral Vascular α-Adrenergic Responsiveness , 2000 .

[27]  B. Kobilka,et al.  Two functionally distinct α2-adrenergic receptors regulate sympathetic neurotransmission , 1999, Nature.

[28]  F. Leslie,et al.  Gender difference in levels of α2-adrenoceptor mRNA in the rat tail artery , 1999 .

[29]  L. Fraenkel,et al.  The Association of Estrogen Replacement Therapy and the Raynaud Phenomenon in Postmenopausal Women , 1998, Annals of Internal Medicine.

[30]  J. Cooke,et al.  Role of Digital Artery Adrenoceptors in Raynaud's Disease , 1997, Vascular medicine.

[31]  T Moore,et al.  Increased nailfold capillary dimensions in primary Raynaud's phenomenon and systemic sclerosis. , 1996, British journal of rheumatology.

[32]  C. Bunker,et al.  Calcitonin gene‐related peptide, endothelin‐1, the cutaneous microvasculature and Raynaud's phenomenon , 1996, The British journal of dermatology.

[33]  F. Sundler,et al.  Occurrence and distribution of peptidergic nerve fibers in skin biopsies from patients with systemic sclerosis. , 1996, Acta dermato-venereologica.

[34]  M. Mayes,et al.  Blockade of Vasospastic Attacks by α2-Adrenergic but Not α1-Adrenergic Antagonists in Idiopathic Raynaud’s Disease , 1995 .

[35]  B. Weber,et al.  Substance P and vasoactive intestinal peptide in patients with progressive systemic sclerosis. Plasma levels before and after autogenic training , 1995 .

[36]  I. Ringqvist,et al.  Sympathetic activation after two weeks of nifedipine treatment in primary Raynaud's patients and controls , 1993, Cardiovascular Drugs and Therapy.

[37]  C. Bunker,et al.  Calcitonin gene-related peptide in treatment of severe peripheral vascular insufficiency in Raynaud's phenomenon , 1993, The Lancet.

[38]  R. Ekman,et al.  Gastrointestinal regulatory peptides in systemic sclerosis. , 1993, Arthritis and rheumatism.

[39]  D. W. Gray,et al.  Human α‐calcitonin gene‐related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide , 1992, British journal of pharmacology.

[40]  D. W. Gray,et al.  Nitric oxide synthesis inhibitors attenuate calcitonin gene-related peptide endothelium-dependent vasorelaxation in rat aorta. , 1992, European journal of pharmacology.

[41]  D. Bylund.  Subtypes of α1‐ and α2‐adrenergic receptors , 1992 .

[42]  B. Hazleman,et al.  Prolonged effect of CGRP in Raynaud's patients: a double-blind randomised comparison with prostacyclin. , 1991, British journal of clinical pharmacology.

[43]  C. Bunker,et al.  Image analysis quantification of peptide‐immunoreactive nerves in the skin of patients with Raynaud's phenomenon and systemic sclerosis , 1991, The Journal of pathology.

[44]  S. Bloom,et al.  Calcitonin gene related peptide. , 1991, BMJ.

[45]  C. Bunker,et al.  Deficiency of calcitonin gene-related peptide in Raynaud's phenomenon , 1990, The Lancet.

[46]  M. Matucci-Cerinic,et al.  Local venomotor response to intravenous infusion of substance P and glyceryl trinitrate in systemic sclerosis. , 1990, Clinical and experimental rheumatology.

[47]  J P Cooke,et al.  Sex differences in control of cutaneous blood flow. , 1990, Circulation.

[48]  B. Hazleman,et al.  SELECTIVE SUPRASENSITIVITY TO CALCITONIN-GENE-RELATED PEPTIDE IN THE HANDS IN RAYNAUD'S PHENOMENON , 1989, The Lancet.

[49]  R. Cohen,et al.  Role of alpha‐adrenoceptor subtypes mediating sympathetic vasoconstriction in human digits , 1988, European journal of clinical investigation.

[50]  R. Håkanson,et al.  Effects of substance P, neurokinin A and calcitonin gene-related peptide in human skin and their involvement in sensory nerve-mediated responses. , 1987, European journal of pharmacology.

[51]  J. Cooke,et al.  Human postjunctional alpha-1 and alpha-2 adrenoceptors: differential distribution in arteries of the limbs. , 1987, The Journal of pharmacology and experimental therapeutics.

[52]  N. Flavahan,et al.  Cooling and alpha 1- and alpha 2-adrenergic responses in cutaneous veins: role of receptor reserve. , 1985, The American journal of physiology.

[53]  G. Rodnan,et al.  Morphologic changes in the digital arteries of patients with progressive systemic sclerosis (scleroderma) and Raynaud phenomenon. , 1980, Medicine.

[54]  P. Molinoff,et al.  beta1- and beta2-Adrenergic receptors in rat cerebral cortex are independently regulated. , 1979, Science.

[55]  P. Dowd,et al.  Raynaud's Disease , 1900, The Lancet.

[56]  L. Czirják,et al.  Investigation of sensory neurogenic components in a bleomycin-induced scleroderma model using transient receptor potential vanilloid 1 receptor- and calcitonin gene-related peptide-knockout mice. , 2008, Arthritis and rheumatism.

[57]  S. Jimenez,et al.  Statins and the vasculopathy of systemic sclerosis: potential therapeutic agents? , 2006, Autoimmunity reviews.

[58]  A. Somlyo,et al.  Signal transduction through the RhoA/Rho-kinase pathway in smooth muscle. , 2004, Journal of muscle research and cell motility.

[59]  A. Tøttrup,et al.  Endothelium-dependent responses in small human mesenteric arteries. , 2004, Physiological research.

[60]  A. Herrick,et al.  The emerging problem of oxidative stress and the role of antioxidants in systemic sclerosis. , 2001, Clinical and experimental rheumatology.

[61]  M. Mayes,et al.  Abnormal responses to endothelial agonists in Raynaud's phenomenon and scleroderma. , 2001, The Journal of rheumatology.

[62]  M. Caron,et al.  Recent advances in the molecular biology of dopamine receptors. , 1993, Annual review of neuroscience.

[63]  I. Lygren,et al.  Lower plasma levels of some gastrointestinal peptides in Raynaud's disease. Influence of transcutaneous nerve stimulation. , 1985, General pharmacology.

[64]  A. Bollinger,et al.  Finger blood flow in healthy subjects of different age and sex and in patients with primary Raynaud's disease. , 1976, Acta chirurgica Scandinavica. Supplementum.