Nitric oxide‐mediated signal transmission in bladder vasculature as a therapeutic target of PDE5 inhibitors: Rodent model studies

2020 ◽  
Author(s):  
Hidekazu Tanaka ◽  
Retsu Mitsui ◽  
Mitsuhiro Oishi ◽  
Stefan Passlick ◽  
Ronald Jabs ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Therapeutic Target ◽  
Signal Transmission ◽  
Rodent Model ◽  
Pde5 Inhibitors ◽  
Model Studies

Nitric oxide synthase uncoupling: A therapeutic target in cardiovascular diseases

2012 ◽  
Vol 57 (5-6) ◽  
pp. 168-172 ◽  
Author(s):  
Nathan D. Roe ◽  
Jun Ren
Keyword(s):  
Nitric Oxide ◽  
Cardiovascular Diseases ◽  
Nitric Oxide Synthase ◽  
Therapeutic Target ◽  
Oxide Synthase

scholarly journals The effect of ethanol on the mechanisms of liver antioxidant defence – a review of rodent model studies

2020 ◽  
Vol 33 (1) ◽  
pp. 79-94
Author(s):  
Aleksandra Kołota
Keyword(s):  
Rodent Model ◽  
Antioxidant Defence ◽  
Model Studies

scholarly journals From animal models to patients: the role of placental microRNAs, miR-210, miR-126, and miR-148a/152 in preeclampsia

2020 ◽  
Vol 134 (8) ◽  
pp. 1001-1025 ◽  
Author(s):  
Sonya Frazier ◽  
Martin W. McBride ◽  
Helen Mulvana ◽  
Delyth Graham
Keyword(s):  
Animal Models ◽  
Cell Types ◽  
Rodent Model ◽  
Hypertensive Disorder ◽  
Model Studies ◽  
Genetic Components ◽  
Immune Mediated ◽  
Hypertensive Disorder Of Pregnancy

Abstract Placental microRNAs (miRNAs) regulate the placental transcriptome and play a pathological role in preeclampsia (PE), a hypertensive disorder of pregnancy. Three PE rodent model studies explored the role of placental miRNAs, miR-210, miR-126, and miR-148/152 respectively, by examining expression of the miRNAs, their inducers, and potential gene targets. This review evaluates the role of miR-210, miR-126, and miR-148/152 in PE by comparing findings from the three rodent model studies with in vitro studies, other animal models, and preeclamptic patients to provide comprehensive insight into genetic components and pathological processes in the placenta contributing to PE. The majority of studies demonstrate miR-210 is upregulated in PE in part driven by HIF-1α and NF-κBp50, stimulated by hypoxia and/or immune-mediated processes. Elevated miR-210 may contribute to PE via inhibiting anti-inflammatory Th2-cytokines. Studies report an up- and downregulation of miR-126, arguably reflecting differences in expression between cell types and its multifunctional capacity. MiR-126 may play a pro-angiogenic role by mediating the PI3K-Akt pathway. Most studies report miR-148/152 family members are upregulated in PE. Evidence suggests they may inhibit DNA methylation of genes involved in metabolic and inflammatory pathways. Given the genetic heterogeneity of PE, it is unlikely that a single placental miRNA is a suitable therapeutic target for all patients. Investigating miRNAs in PE subtypes in patients and animal models may represent a more appropriate approach going forward. Developing methods for targeting placental miRNAs and specific placental cell types remains crucial for research seeking to target placental miRNAs as a novel treatment for PE.

scholarly journals Regulation of DDAH1 as a Potential Therapeutic Target for Treating Cardiovascular Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Xiaoyu Liu ◽  
John Fassett ◽  
Yidong Wei ◽  
Yingjie Chen
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Congestive Heart Failure ◽  
Cardiovascular Diseases ◽  
Therapeutic Target ◽  
Farnesoid X Receptor ◽  
Nitric Oxide Synthase Inhibitor ◽  
Endogenous Nitric Oxide ◽  
Synthase Inhibitor ◽  
Nitric Oxide Bioavailability

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor that blocks nitric oxide production, while congestive heart failure is associated with increased plasma and tissue ADMA content. Increased plasma ADMA is a strong and independent predictor of all-cause mortality in the community and the strongest predictor of mortality in patients after myocardial infarction. Recent studies demonstrated that dimethylarginine dimethylaminohydrolase-1 (DDAH1) is the critical enzyme for ADMA degradation and thereby plays an important role in maintaining cardiovascular nitric oxide bioavailability. Interestingly, activation of the farnesoid X receptor (FXR) through the bile acid ursodeoxycholic acid (UDCA) or synthetic FXR agonists, such as GW4064, can increase DDAH1 expression. Thus, modulating DDAH1 activity through FXR receptor agonists such as UDCA could be a therapeutic target for treating reduced nitric oxide bioavailability in congestive heart failure and other cardiovascular diseases.

Rho-kinase as a therapeutic target in vascular diseases: Striking nitric oxide signaling

Nitric Oxide ◽  
2014 ◽  
Vol 43 ◽  
pp. 45-54 ◽  
Author(s):  
Gopi Krishna Kolluru ◽  
Syamantak Majumder ◽  
Suvro Chatterjee
Keyword(s):  
Nitric Oxide ◽  
Therapeutic Target ◽  
Rho Kinase ◽  
Vascular Diseases ◽  
Nitric Oxide Signaling

scholarly journals Potential of Inducible Nitric Oxide Synthase as a Therapeutic Target for Allergen-Induced Airway Hyperresponsiveness: A Critical Connection to Nitric Oxide Levels and PARP Activity

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Salome’ V. Ibba ◽  
Mohamed A. Ghonim ◽  
Kusma Pyakurel ◽  
Matthew R. Lammi ◽  
Anil Mishra ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Therapeutic Target ◽  
Airway Hyperresponsiveness ◽  
Mononuclear Cells ◽  
Inos Expression ◽  
Parp Inhibition ◽  
Protein Nitration ◽  
Parp Activation ◽  
Peripheral Blood Mononuclear ◽  
Inos Inhibitors

Although expression of inducible NO synthase (iNOS) in the lungs of asthmatics and associated nitrosative damage are established, iNOS failed as a therapeutic target for blocking airway hyperresponsiveness (AHR) and inflammation in asthmatics. This dichotomy calls for better strategies with which the enzyme is adequately targeted. Here, we confirm iNOS expression in the asthmatic lung with concomitant protein nitration and poly(ADP-ribose) polymerase (PARP) activation. We show, for the first time, that iNOS is highly expressed in peripheral blood mononuclear cells (PBMCs) of asthmatics with uncontrolled disease, which did not correspond to protein nitration. Selective iNOS inhibition with L-NIL protected against AHR upon acute, but not chronic, exposure to ovalbumin or house dust mite (HDM) in mice. Supplementation of NO by nitrite administration significantly blocked AHR in chronically HDM-exposed mice that were treated with L-NIL. Protection against chronic HDM exposure-induced AHR by olaparib-mediated PARP inhibition may be associated with the partial but not the complete blockade of iNOS expression. Indeed, L-NIL administration prevented olaparib-mediated protection against AHR in chronically HDM-exposed mice. Our study suggests that the amount of iNOS and NO are critical determinants in the modulation of AHR by selective iNOS inhibitors and renews the potential of iNOS as a therapeutic target for asthma.

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