INT8662

Context Info Confidence 0.70 First Reported 1990 Last Reported 2010 Negated 2 Speculated 4 Reported most in Body Documents 144 Total Number 148 Disease Relevance 125.34 Pain Relevance 19.59

extracellular space (EDN1) extracellular region (EDN1) cell-cell signaling (EDN1) cytoplasm (EDN1)

Anatomy Link Frequency plasma 23 blood 5 heart 5 endothelial cells 4 chondrocytes 3 EDN1 (Homo sapiens)

Pain Link Frequency Relevance Heat Inflammation 638 100.00 Angina 94 99.90 anesthesia 12 99.84 Pain 157 99.74 Multiple sclerosis 48 99.72 Serotonin 36 99.64 antagonist 851 99.56 Osteoarthritis 560 99.52 Kinase C 89 99.50 Calcium channel 124 99.32

Disease Link Frequency Relevance Heat INFLAMMATION 728 100.00 Myocardial Infarction 261 100.00 Blister 115 100.00 Increased Venous Pressure Under Development 1900 99.96 Cardiovascular Disease 264 99.92 Diabetic Angiopathy 159 99.92 Disease 1041 99.90 Insulin Resistance 246 99.90 Cv General 3 Under Development 154 99.90 Pulmonary Hypertension 1932 99.88

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Speculation

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Disease term

Delayed elevation of plasma endothelin-1 during unilateral alveolar hypoxia without systemic hypoxemia in humans.

Positive_regulation (elevation) of endothelin-1 in plasma associated with anesthesia and hypoxia

1) Confidence 0.70 Published 1997 Journal Acta Anaesthesiol Scand Section Title Doc Link 9062613 Disease Relevance 0.38 Pain Relevance 0.10

CONCLUSIONS: Tissue ischemia may increase venous ET-1 levels in humans.

Spec (may) Positive_regulation (increase) of ET-1

2) Confidence 0.70 Published 1995 Journal J. Cardiothorac. Vasc. Anesth. Section Body Doc Link 8547550 Disease Relevance 0 Pain Relevance 0

Immediately after the initial release of the proximal and distal clamps, venous oxygen content dramatically decreased from 11.3 to 3.6 mL/dL (vol%) with significant increases in venous ET-1 concentration from 2.3 to 4.9 pg/mL.

Positive_regulation (increases) of ET-1 in proximal

3) Confidence 0.70 Published 1995 Journal J. Cardiothorac. Vasc. Anesth. Section Body Doc Link 8547550 Disease Relevance 0 Pain Relevance 0

CONCLUSIONS: We conclude that there might be an ischemic component in this patient with optic neuritis and hypothesize that this ischemic component is at least in part due to a temporarily increased endothelin-1 level.

Positive_regulation (increased) of endothelin-1 in optic

4) Confidence 0.70 Published 2003 Journal Ophthalmologica Section Body Doc Link 14573982 Disease Relevance 0.08 Pain Relevance 0

Infusion of HS-HES resulted in an increase in plasma endothelin concentration before and after CPB (from 3 to 6 pg/mL).

Positive_regulation (increase) of endothelin in plasma

5) Confidence 0.67 Published 1994 Journal J. Cardiothorac. Vasc. Anesth. Section Abstract Doc Link 7520297 Disease Relevance 0.08 Pain Relevance 0.12

Thus, plasma endothelin level was elevated in patients with unstable angina pectoris and myocardial infarction and the increase persisted for several days after the onset of symptoms.

Positive_regulation (elevated) of endothelin in plasma associated with angina and myocardial infarction

6) Confidence 0.67 Published 1999 Journal Cardiology Section Abstract Doc Link 10449883 Disease Relevance 0.88 Pain Relevance 0.63

They point to the observation of significantly elevated ET-1 levels in vasospastic and systemic diseases such as multiple sclerosis, rheumatoid arthritis, fibromyalgia, and Susac syndrome.

Positive_regulation (elevated) of ET-1 associated with susac syndrome, multiple sclerosis, rheumatoid arthritis, disease and fibrositis

7) Confidence 0.66 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699797 Disease Relevance 1.10 Pain Relevance 0.25

Although animal models have suggested that increased levels of ET-1 by itself can lead to glaucoma via ischemia (Cioffi et al 2004), these same results have not been demonstrated in human population studies.

Positive_regulation (increased) of ET-1 associated with ischemia and glaucoma

8) Confidence 0.66 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699797 Disease Relevance 1.39 Pain Relevance 0.21

Several studies show that calcium channel antagonists reduce the effect of increased levels of ET-1 on ocular perfusion and improve visual field defects through induced vasodilation (Flammer et al 2001).

Positive_regulation (increased) of ET-1 associated with scotoma, antagonist, calcium channel and increased venous pressure under development

9) Confidence 0.66 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699797 Disease Relevance 1.52 Pain Relevance 0.61

Grieshaber and Flammer (2005) suggest that the elevation of ET-1 in glaucoma represents an epiphenomenon rather than a distinctive mechanism.

Positive_regulation (elevation) of ET-1 associated with glaucoma

10) Confidence 0.66 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699797 Disease Relevance 0.93 Pain Relevance 0.21

Interestingly, the increase in CBV during selective ETA receptor blockade was more pronounced in type 2 diabetic patients with a high body mass index (BMI) and low levels of insulin-like growth factor binding protein-1 (IGFBP-1), supporting the existence of a close relationship between insulin resistance and increased ET-1 activity.

Positive_regulation (increased) of ET-1 in body associated with diabetes mellitus, obesity and insulin resistance

11) Confidence 0.66 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2605330 Disease Relevance 0.94 Pain Relevance 0.05

This supports the notion that the ET-1 system is upregulated in patients with type 2 diabetes and that ETA receptor blockade exerts hemodynamic effects only under such conditions.

Positive_regulation (upregulated) of ET-1 associated with diabetes mellitus

12) Confidence 0.66 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2605330 Disease Relevance 0.91 Pain Relevance 0.05

Here we show that in a murine osteolytic 2472 sarcoma model of bone cancer pain, the 2472 sarcoma cells express high levels of ET-1, but express low or undetectable levels of endothelin A (ETAR) or B (ETBR) receptors whereas a subpopulation of sensory neurons express the ETAR and non-myelinating Schwann cells express the ETBR.

Positive_regulation (levels) of ET-1 in sensory neurons associated with sarcoma and cancer pain

13) Confidence 0.66 Published 2004 Journal Neuroscience Section Abstract Doc Link 15207337 Disease Relevance 1.16 Pain Relevance 0.60

Additionally, we have recently demonstrated that ET-1 is significantly increased locally in OA cartilage and synovial membrane when compared with normal tissues.

Positive_regulation (increased) of ET-1 in cartilage associated with osteoarthritis

14) Confidence 0.62 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1065327 Disease Relevance 0.41 Pain Relevance 0.23

RESULTS: The patient was found to have a temporary ocular blood flow dysregulation and increased plasma endothelin-1 levels which decreased after the acute phase of the optic nerve.

Positive_regulation (increased) of endothelin-1 in optic nerve

15) Confidence 0.61 Published 2003 Journal Ophthalmologica Section Body Doc Link 14573982 Disease Relevance 0.09 Pain Relevance 0

In venous plasma of patients with erectile dysfunction, significantly increased ET-1 and decreased NO levels were found [32].

Positive_regulation (increased) of ET-1 in plasma associated with reprotox - general 2

16) Confidence 0.60 Published 2006 Journal BMC Musculoskelet Disord Section Body Doc Link PMC1693561 Disease Relevance 0.96 Pain Relevance 0.38

In addition, in postmenopausal women, long-term ERT decreased plasma ET-1 levels in the systematic circulation, associated with an increased NO-to-ET-1 ratio (Polderman et al 1993; Lieberman et al 1994).

Positive_regulation (increased) of NO-to-ET-1 in plasma

17) Confidence 0.59 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2515431 Disease Relevance 0.09 Pain Relevance 0.07

Most patients with pulmonary artery hypertension have elevated EDN1 levels, and pharmacological blockage of EDN1 activity leads to clinical improvement and better prognosis [81].

Positive_regulation (elevated) of EDN1 in pulmonary artery associated with hypertension

18) Confidence 0.58 Published 2007 Journal PLoS Genetics Section Body Doc Link PMC1994710 Disease Relevance 0.91 Pain Relevance 0.08

Aqueous humor levels of ET-1 are reportedly elevated in HTG (Noske et al 1997) and one study demonstrated a significant elevation of plasma ET-1 in HTG when the subjects were moved from the supine to upright position (Kaiser et al 1997).

Positive_regulation (elevation) of ET-1 in plasma associated with glaucoma

19) Confidence 0.58 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699797 Disease Relevance 0.88 Pain Relevance 0

To further support a role for vasospasm in endothelial dysfunction, Nicolela and colleagues (2003) reported an abnormal increase in plasma ET-1 in response to body cooling in OAG patients.

Positive_regulation (increase) of ET-1 in plasma associated with glaucoma and increased venous pressure under development

20) Confidence 0.58 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699797 Disease Relevance 0.69 Pain Relevance 0

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