RGD Reference Report - Modafinil improves monocrotaline-induced pulmonary hypertension rat model. - Rat Genome Database

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Modafinil improves monocrotaline-induced pulmonary hypertension rat model.

Authors: Lee, Hyeryon  Kim, Kwan Chang  Cho, Min-Sun  Suh, Suk-Hyo  Hong, Young Mi 
Citation: Lee H, etal., Pediatr Res. 2016 Jul;80(1):119-27. doi: 10.1038/pr.2016.38. Epub 2016 Mar 9.
RGD ID: 329969898
Pubmed: PMID:26959484   (View Abstract at PubMed)
DOI: DOI:10.1038/pr.2016.38   (Journal Full-text)


BACKGROUND: Pulmonary arterial hypertension (PAH) progressively leads to increases in pulmonary vasoconstriction. Modafinil plays a role in vasorelaxation and blocking KCa3.1 channel with a result of elevating intracellular cyclic adenosine monophosphate (cAMP) levels. The purpose of this study is to evaluate the effects on modafinil in monocrotaline (MCT)-induced PAH rat.
METHODS: The rats were separated into three groups: the control group, the monocrotaline (M) group (MCT 60 mg/kg), and the modafinil (MD) group (MCT 60 mg/kg + modafinil).
RESULTS: Reduced right ventricular pressure (RVP) was observed in the MD group. Right ventricular hypertrophy was improved in the MD group. Reduced number of intra-acinar pulmonary arteries and medial wall thickness were noted in the MD group. After the administration of modafinil, protein expressions of endothelin-1 (ET-1), endothelin receptor A (ERA) and KCa3.1 channel were significantly reduced. Modafinil suppressed pulmonary artery smooth muscle cell (PASMC) proliferation via cAMP and KCa3.1 channel. Additionally, we confirmed protein expressions such as Bcl-2-associated X, vascular endothelial growth factor, tumor necrosis factor-α, and interleukin-6 were reduced in the MD group.
CONCLUSION: Modafinil improved PAH by vasorelaxation and a decrease in medial thickening via ET-1, ERA, and KCa3.1 down regulation. This is a meaningful study of a modafinil in PAH model.



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Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
BAXHumanRight Ventricular Hypertrophy treatmentISOBax (Rattus norvegicus)associated with Pulmonary Arterial HypertensionRGD 
BaxMouseRight Ventricular Hypertrophy treatmentISOBax (Rattus norvegicus)associated with Pulmonary Arterial HypertensionRGD 
BaxRatRight Ventricular Hypertrophy treatmentIEP associated with Pulmonary Arterial HypertensionRGD 
IL6HumanRight Ventricular Hypertrophy treatmentISOIl6 (Rattus norvegicus)associated with pulmonary arterial hypertensionRGD 
Il6MouseRight Ventricular Hypertrophy treatmentISOIl6 (Rattus norvegicus)associated with pulmonary arterial hypertensionRGD 
Il6RatRight Ventricular Hypertrophy treatmentIEP associated with pulmonary arterial hypertensionRGD 
KCNN4HumanRight Ventricular Hypertrophy treatmentISOKcnn4 (Rattus norvegicus)associated with Pulmonary Arterial HypertensionRGD 
Kcnn4MouseRight Ventricular Hypertrophy treatmentISOKcnn4 (Rattus norvegicus)associated with Pulmonary Arterial HypertensionRGD 
Kcnn4RatRight Ventricular Hypertrophy treatmentIEP associated with Pulmonary Arterial HypertensionRGD 
TNFHumanRight Ventricular Hypertrophy treatmentISOTnf (Rattus norvegicus)associated with Pulmonary Arterial HypertensionRGD 
TnfRatRight Ventricular Hypertrophy treatmentIEP associated with Pulmonary Arterial HypertensionRGD 
TnfMouseRight Ventricular Hypertrophy treatmentISOTnf (Rattus norvegicus)associated with Pulmonary Arterial HypertensionRGD 
VEGFAHumanRight Ventricular Hypertrophy treatmentISOVegfa (Rattus norvegicus)associated with Pulmonary arterial hypertensionRGD 
VegfaRatRight Ventricular Hypertrophy treatmentIEP associated with Pulmonary arterial hypertensionRGD 
VegfaMouseRight Ventricular Hypertrophy treatmentISOVegfa (Rattus norvegicus)associated with Pulmonary arterial hypertensionRGD 
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Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
BAXHumanmonocrotaline increases expression ISOBax (Rattus norvegicus)monocrotaline increases expression of Bax protein in lungRGD 
BAXHumanmonocrotaline multiple interactionsISOBax (Rattus norvegicus)modafinil inhibits the reaction [monocrotaline increases expression of Bax protein in lung]RGD 
BaxRatmonocrotaline increases expression EXP monocrotaline increases expression of Bax protein in lungRGD 
BaxMousemonocrotaline multiple interactionsISOBax (Rattus norvegicus)modafinil inhibits the reaction [monocrotaline increases expression of Bax protein in lung]RGD 
BaxMousemonocrotaline increases expression ISOBax (Rattus norvegicus)monocrotaline increases expression of Bax protein in lungRGD 
BaxRatmonocrotaline multiple interactionsEXP modafinil inhibits the reaction [monocrotaline increases expression of Bax protein in lung]RGD 
IL6Humanmonocrotaline multiple interactionsISOIl6 (Rattus norvegicus)modafinil inhibits the reaction [monocrotaline increases expression of Il6 protein in lung]RGD 
IL6Humanmonocrotaline treatmentISOIl6 (Rattus norvegicus)monocrotaline increases expression of Il6 protein in lungRGD 
Il6Ratmonocrotaline multiple interactionsEXP modafinil inhibits the reaction [monocrotaline increases expression of Il6 protein in lung]RGD 
Il6Mousemonocrotaline treatmentISOIl6 (Rattus norvegicus)monocrotaline increases expression of Il6 protein in lungRGD 
Il6Mousemonocrotaline multiple interactionsISOIl6 (Rattus norvegicus)modafinil inhibits the reaction [monocrotaline increases expression of Il6 protein in lung]RGD 
Il6Ratmonocrotaline treatmentEXP monocrotaline increases expression of Il6 protein in lungRGD 
KCNN4Humanmonocrotaline increases expression ISOKcnn4 (Rattus norvegicus)monocrotaline increases expression of Kcnn4 protein in lung and smooth muscle cell of the pulmonary arteryRGD 
KCNN4Humanmonocrotaline multiple interactionsISOKcnn4 (Rattus norvegicus)modafinil inhibits the reaction [monocrotaline increases expression of Kcnn4 protein in lung and smooth muscle cell of the pulmonary artery]RGD 
Kcnn4Ratmonocrotaline increases expression EXP monocrotaline increases expression of Kcnn4 protein in lung and smooth muscle cell of the pulmonary arteryRGD 
Kcnn4Mousemonocrotaline multiple interactionsISOKcnn4 (Rattus norvegicus)modafinil inhibits the reaction [monocrotaline increases expression of Kcnn4 protein in lung and smooth muscle cell of the pulmonary artery]RGD 
Kcnn4Mousemonocrotaline increases expression ISOKcnn4 (Rattus norvegicus)monocrotaline increases expression of Kcnn4 protein in lung and smooth muscle cell of the pulmonary arteryRGD 
Kcnn4Ratmonocrotaline multiple interactionsEXP modafinil inhibits the reaction [monocrotaline increases expression of Kcnn4 protein in lung and smooth muscle cell of the pulmonary artery]RGD 
TNFHumanmonocrotaline increases expression ISOTnf (Rattus norvegicus)monocrotaline increases expression of Tnf protein in lungRGD 
TNFHumanmonocrotaline multiple interactionsISOTnf (Rattus norvegicus)modafinil inhibits the reaction [monocrotaline increases expression of Tnf protein in lung]RGD 

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Genes (Rattus norvegicus)
Bax  (BCL2 associated X, apoptosis regulator) Il6  (interleukin 6) Kcnn4  (potassium calcium-activated channel subfamily N member 4)
Tnf  (tumor necrosis factor) Vegfa  (vascular endothelial growth factor A)

Genes (Mus musculus)
Bax  (BCL2-associated X protein) Il6  (interleukin 6) Kcnn4  (potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4)
Tnf  (tumor necrosis factor) Vegfa  (vascular endothelial growth factor A)

Genes (Homo sapiens)
BAX  (BCL2 associated X, apoptosis regulator) IL6  (interleukin 6) KCNN4  (potassium calcium-activated channel subfamily N member 4)
TNF  (tumor necrosis factor) VEGFA  (vascular endothelial growth factor A)