Involvement of G proteins and Rho kinase in α1-Adrenoceptor mediated contractions of rat portal vein.

2020 ◽  
Author(s):  
Hadeel A. Alsufyani ◽  
James R. Docherty
Keyword(s):  
Portal Vein ◽  
G Proteins ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Adrenoceptor Antagonist ◽  
Rat Portal Vein ◽  
Low Concentrations ◽  
Adrenoceptor Agonist ◽  
Rho Kinase Inhibitor

Contractions of rat portal vein in response to the α1-adrenoceptor agonist phenylephrine consist of phasic contractions at low concentrations, with tonic contractions superimposed at higher concentrations. The α1D-adrenoceptor antagonist BMY7378 (7.0, -log M) did not affect phasic or tonic contractions to phenylephrine. The relatively non-selective α1-adrenoceptor antagonist prazosin (7.5) shifted equally the potencies of phenylephrine at producing phasic and tonic contractions, with pKB values of 8.85 and 8.83 (-log M), respectively. The α1A-adrenoceptor antagonist RS100329 (8.5) produced a significantly greater shift in phenylephrine potency for phasic (pKB of 10.51) than tonic contractions (pKB of 9.78). Prazosin was less effective than RS100329 at reducing the effects of phenylphrine on frequency of phasic contractions. The Rho kinase inhibitor fasudil (5.0) did not affect phasic contractions to phenylephrine, but significantly reduced tonic contractions. It is concluded that there is no evidence for involvement of α1D-adrenoceptors in responses of rat portal vein to phenylephrine, but phasic responses involve predominantly α1A-adrenoceptors. Tonic responses may involve predominantly α1B-adrenoceptors, and are at least partly mediated by mechanisms involving Rho kinase sensitive to fasudil.

Rho kinase is involved in Ca2+ entry of rat penile small arteries

2008 ◽  
Vol 294 (4) ◽  
pp. H1923-H1932 ◽  
Author(s):  
Nuria Villalba ◽  
Edgaras Stankevicius ◽  
Ulf Simonsen ◽  
Dolores Prieto
Keyword(s):  
Kinase Inhibitor ◽  
Physiological Activity ◽  
Rho Kinase ◽  
Cyclopiazonic Acid ◽  
Erectile Tissue ◽  
Kinase C ◽  
Adrenoceptor Agonist ◽  
Rho Kinase Inhibitor ◽  
Intracellular Ca ◽  
Penile Arteries

Tonic physiological activity of RhoA/Rho kinase contributes to the maintenance of penile flaccidity through its involvement in the Ca2+ sensitization of erectile tissue smooth muscle. The present study hypothesized that Rho kinase is also involved in the modulation of Ca2+ entry induced by α1-adrenoceptor stimulation of penile arteries. Rat penile arteries were mounted in microvascular myographs for simultaneous measurements of intracellular Ca2+ ([Ca2+]i) and force. The Rho-kinase inhibitor Y-27632 markedly reduced norepinephrine-mediated electrically induced contractions and the increases in both [Ca2+]i and tension elicited by the α1-adrenoceptor agonist phenylephrine (Phe). In contrast, the protein kinase C (PKC) inhibitor Ro-31-8220 reduced tension without altering the Phe-induced increase in [Ca2+]i. In the presence of nifedipine, Y-27632 still inhibited the non-L-type Ca2+ signal and blunted Phe contraction. Y-27632 did not impair the capacitative Ca2+ entry evoked by store depletion with cyclopiazonic acid but largely reduced the Ba2+ influx stimulated by Phe in fura-2 AM-loaded arteries. The addition of Y-27632 to arteries depolarized with high KCl markedly reduced tension without changing [Ca2+]i. In α-toxin-permeabilized penile arteries stimulated with threshold Ca2+ concentrations, Y-27632 inhibited the sensitization induced by either guanosine 5′- O-(3-thiotriphosphate) (GTPγS) or Phe in the presence of GTPγS. However, Y-27632 failed to alter contractions induced by a maximal concentration of free Ca2+. These results suggest that Rho kinase, besides its contribution to the Ca2+ sensitization of the contractile proteins, is also involved in the regulation of Ca2+ entry through a nonselective cation channel activated by α1-adenoceptor stimulation in rat penile arteries.

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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