scholarly journals Ripasudil Endgame: Role of Rho-Kinase Inhibitor as a Last-Ditch-Stand Towards Maximally Tolerated Medical Therapy to a Patient of Advanced Glaucoma

2021 ◽  
Vol Volume 15 ◽  
pp. 2683-2692
Author(s):  
Mayuresh Naik ◽  
Monika Kapur ◽  
VishnuSwarup Gupta ◽  
HarinderSingh Sethi ◽  
Kartikeya Srivastava
Keyword(s):  
Medical Therapy ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Rho Kinase Inhibitor ◽  
Advanced Glaucoma

scholarly journals Resveratrol’s Impact on Vascular Smooth Muscle Cells Hyporeactivity: The Role of Rho-Kinase Inhibition

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Michał Wiciński ◽  
Bartosz Malinowski ◽  
Paweł Rajewski ◽  
Paweł Szychta ◽  
Eryk Wódkiewicz ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinases ◽  
Vascular Smooth Muscle Cells ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Pressure Effects ◽  
Kinase Inhibition ◽  
Rho Kinase Inhibitor ◽  
Dependent Protein

Resveratrol (3,5,4′-trihydroxystilbene) is a chemical compound belonging to the group of polyphenols and flavonoids. The aim of the present study was to determine the influence of resveratrol application along with certain modulating factors, such as 8Br-cGMP-activator of cGMP-dependent protein kinases, HA-1077-Rho-kinase inhibitor, and Bay K8644-calcium channel agonist, on VMSCs constriction triggered by phenylephrine. Resveratrol at a dose of 10 mg/kg/24 h administered for 4 weeks reduced the reactivity of the arteries to the pressure action of catecholamines. Tests performed after four weeks of resveratrol administration showed that 8Br-cGMP at the concentrations of 0.01 mM/l and 0.1 mM/l intensifies this effect. Simultaneous resveratrol and Bay K8644 administration led to a significant decrease in contractility compared to the vessels collected from animals (Res−). This effect was dependent on the concentration of Bay K8644. Resveratrol seems to be counteractive against Bay K8644 by blocking L-type calcium channels. As the concentration of HA-1077 increased, there was a marked hyporeactivity of the vessels to the pressure effects of phenylephrine. The results indicate synergy between resveratrol and Rho-kinase inhibition.

Rho-kinase Is Involved in the Sustained Phosphorylation of Myosin and the Irreversible Platelet Aggregation Induced by PAR1 Activating Peptide

2001 ◽  
Vol 85 (03) ◽  
pp. 514-520 ◽  
Author(s):  
K. Missy ◽  
M. Plantavid ◽  
C. Viala ◽  
H. Chap ◽  
P. Pacaud ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Serotonin Secretion ◽  
Platelet Disaggregation ◽  
Rho Kinase Inhibitor ◽  
Early Peak ◽  
Mlc Phosphorylation ◽  
Dose Dependent ◽  
Sustained Phosphorylation

SummaryWe have addressed the role of Rho-kinase in the different steps of thrombin receptor agonist peptide (TRAP) -induced platelet activation. Interestingly, under physiological conditions, incubation of platelets with increasing concentrations of the specific Rho-kinase inhibitor Y-27632 resulted in a dose-dependent reversion of the aggregation induced by 10 μM TRAP, without affecting serotonin secretion. Addition of Y-27632 after three minutes of TRAP stimulation, when the maximal aggregation was reached, resulted in a rapid disaggregation of platelets. Accordingly, the early peak of myosin light chain (MLC) phosphorylation induced by TRAP was not affected by Y-27632 but its sustained phosphorylation, observed during the irreversible phase of aggregation, was dependent of Rho-kinase activity. The rapid decrease in MLC phosphorylation upon Y-27632 treatment correlated well with the specific disappearance of myosin heavy chain from the cytoskeleton and preceded platelet disaggregation. Finally, we provide evidence that secreted ADP, known to play a key role in TRAP-induced irreversible phase of aggregation, was involved in the sustained MLC phosphorylation through Rho-kinase and could be replaced by epinephrine.

scholarly journals Rac1 functions as a reversible tension modulator to stabilize VE-cadherin trans-interaction

2015 ◽  
Vol 208 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Nazila Daneshjou ◽  
Nathan Sieracki ◽  
Geerten P. van Nieuw Amerongen ◽  
Daniel E. Conway ◽  
Martin A. Schwartz ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Vascular Endothelial ◽  
Adhesive Interaction ◽  
Adhesion Sites ◽  
Vascular Endothelial Cadherin ◽  
Rac1 Activity ◽  
Rho Kinase Inhibitor ◽  
The Relationship

The role of the RhoGTPase Rac1 in stabilizing mature endothelial adherens junctions (AJs) is not well understood. In this paper, using a photoactivatable probe to control Rac1 activity at AJs, we addressed the relationship between Rac1 and the dynamics of vascular endothelial cadherin (VE-cadherin). We demonstrated that Rac1 activation reduced the rate of VE-cadherin dissociation, leading to increased density of VE-cadherin at AJs. This response was coupled to a reduction in actomyosin-dependent tension across VE-cadherin adhesion sites. We observed that inhibiting myosin II directly or through photo-release of the caged Rho kinase inhibitor also reduced the rate of VE-cadherin dissociation. Thus, Rac1 functions by stabilizing VE-cadherin trans-dimers in mature AJs by counteracting the actomyosin tension. The results suggest a new model of VE-cadherin adhesive interaction mediated by Rac1-induced reduction of mechanical tension at AJs, resulting in the stabilization of VE-cadherin adhesions.

Efficacy of the Additional Use of Ripasudil, a Rho-Kinase Inhibitor, in Patients With Glaucoma Inadequately Controlled Under Maximum Medical Therapy

2017 ◽  
Vol 26 (2) ◽  
pp. 96-100 ◽  
Author(s):  
Hiroshi Inazaki ◽  
Satoshi Kobayashi ◽  
Yoko Anzai ◽  
Hisayoshi Satoh ◽  
Shimpei Sato ◽  
...  
Keyword(s):  
Medical Therapy ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Rho Kinase Inhibitor
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