Rho kinase inhibition partly weakens myogenic reactivity in rat small arteries by changing calcium sensitivity

2002 ◽  
Vol 283 (6) ◽  
pp. H2288-H2295 ◽  
Author(s):  
Rudolf Schubert ◽  
Vjatscheslav U. Kalentchuk ◽  
Ulrike Krien
Keyword(s):  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Calcium Sensitivity ◽  
Vessel Diameter ◽  
Myogenic Response ◽  
Small Arteries ◽  
Rho Kinase Inhibitor ◽  
Neural Transmission ◽  
The Relationship ◽  
Rat Tail

The hypothesis that Rho kinase is involved in myogenic reactivity was investigated in pressurized rat tail small arteries using videomicroscopic diameter determination and calcium fluorimetry. The potent Rho kinase inhibitor Y-27632 reversibly increased vessel diameter at 80 mmHg without changing the intracellular calcium concentration ([Ca]i) shifting the relationship between diameter change and [Ca]i to higher calcium levels. Neither endothelium removal nor inhibition of neural transmission affected the Y-27632-induced effect. Y-27632 at 3 × 10−6 mol/l attenuated the myogenic response in the pressure range from 10 to 120 mmHg, shifting the relationship between vessel tone and [Ca]i to higher calcium levels. In addition, the Y-27632-induced shift of the relationship between vessel tone and [Ca]i was larger at 80 than at 10 mmHg. These results suggest that smooth muscle cell Rho kinase in rat tail small arteries 1) is in an active state partly determining the level of the myogenic tone, and 2) alters the strength of the myogenic response by changing calcium sensitivity, probably caused by the pressure-induced activation of the kinase.

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.

scholarly journals Rho-kinase inhibitor hydroxyfasudil protects against HIV-1 Tat-induced dysfunction of tight junction and neprilysin/Aβ transfer receptor expression in mouse brain microvessels

2021 ◽  
Vol 476 (5) ◽  
pp. 2159-2170
Author(s):  
Qiangtang Chen ◽  
Yu Wu ◽  
Yachun Yu ◽  
Junxiang Wei ◽  
Wen Huang
Keyword(s):  
Tight Junction ◽  
Signaling Pathway ◽  
Mouse Brain ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Brain Microvessels ◽  
Rho Kinase Inhibitor ◽  
Hiv 1

AbstractHIV-1 transactivator protein (Tat) induces tight junction (TJ) dysfunction and amyloid-beta (Aβ) clearance dysfunction, contributing to the development and progression of HIV-1-associated neurocognitive disorder (HAND). The Rho/ROCK signaling pathway has protective effects on neurodegenerative disease. However, the underlying mechanisms of whether Rho/ROCK protects against HIV-1 Tat-caused dysfunction of TJ and neprilysin (NEP)/Aβ transfer receptor expression have not been elucidated. C57BL/6 mice were administered sterile saline (i.p., 100 μL) or Rho-kinase inhibitor hydroxyfasudil (HF) (i.p., 10 mg/kg) or HIV-1 Tat (i.v., 100 μg/kg) or HF 30 min before being exposed to HIV-1 Tat once a day for seven consecutive days. Evans Blue (EB) leakage was detected via spectrophotometer and brain slides in mouse brains. The protein and mRNA levels of zonula occludens-1 (ZO-1), occludin, NEP, receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP1) in mouse brain microvessels were, respectively, analyzed by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) analyses. Exposure of the mice to HIV-1 Tat increased the amount of EB leakage, EB fluorescence intensity, blood–brain barrier (BBB) permeability, as well as the RAGE protein and mRNA levels, and decreased the protein and mRNA levels of ZO-1, occludin, NEP, and LRP1 in mouse brain microvessels. However, these effects were weakened by Rho-kinase inhibitor HF. Taken together, these results provide information that the Rho/ROCK signaling pathway is involved in HIV-1 Tat-induced dysfunction of TJ and NEP/Aβ transfer receptor expression in the C57BL/6 mouse brain. These findings shed some light on potentiality of inhibiting Rho/Rock signaling pathway in handling HAND.

Rho kinase inhibitor for primary open-angle glaucoma and ocular hypertension

2020 ◽  
Author(s):  
Josefine Clement Freiberg ◽  
Alexander von Spreckelsen ◽  
Naira Khachatryan ◽  
Miriam Kolko ◽  
Augusto Azuara-Blanco ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
Primary Open Angle Glaucoma ◽  
Kinase Inhibitor ◽  
Open Angle Glaucoma ◽  
Rho Kinase ◽  
Open Angle ◽  
Rho Kinase Inhibitor

Protective effect of hydroxyfasudil, a Rho kinase inhibitor, on ventral prostatic hyperplasia in the spontaneously hypertensive rat

The Prostate ◽  
2015 ◽  
Vol 75 (15) ◽  
pp. 1774-1782 ◽  
Author(s):  
Felix Holmström ◽  
Shogo Shimizu ◽  
Takahiro Shimizu ◽  
Youichirou Higashi ◽  
Darryl T. Martin ◽  
...  
Keyword(s):  
Protective Effect ◽  
Kinase Inhibitor ◽  
Spontaneously Hypertensive Rat ◽  
Rho Kinase ◽  
Prostatic Hyperplasia ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Rho Kinase Inhibitor
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