Different Effect of Rho Kinase Inhibition on Calcium Signaling in Rat Isolated Large and Small Arteries

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

In addition to its role in the regulation of artery contraction, Rho kinase (ROCK) was reported to be involved in the cytosolic calcium response to vasoconstrictor agonists in rat aorta and superior mesenteric artery (SMA). However, it remains to be determined whether ROCK also contributes to calcium signaling in resistance arteries, which play a major role in blood pressure regulation. The investigation of the effect of ROCK inhibition on the calcium and contractile responses of rat resistance mesenteric artery (RMA), in comparison with aorta and SMA, indicated that the calcium response to noradrenaline was inhibited by the ROCK inhibitor Y-27632 in aorta and SMA but not in RMA. The effect of Y-27632 on the calcium signal was unaffected by cytochalasin-D. ROCK activation in noradrenaline-stimulated arteries was confirmed by the inhibition of myosin light chain phosphorylation by Y-27632. Moreover, noradrenaline-induced calcium signaling was similarly inhibited by nimodipine in aorta, SMA and RMA, but nimodipine sensitivity of the contraction increased from the aorta to the RMA, suggesting that the contraction was controlled by different sources of calcium. In pressurized RMA, Y-27632 and H-1152 depressed pressure-induced calcium responses and abolished myogenic contraction. These results stress the important differences in calcium signaling between conductance and resistance arteries.

Related collections

Most cited references 27

Record: found
Abstract: found
Article: not found

Rho-Kinase Phosphorylates COOH-terminal Threonines of Ezrin/Radixin/Moesin (ERM) Proteins and Regulates Their Head-to-Tail Association

Takeshi Matsui, Masato Maeda, Yoshinori Doi … (1998)

The ezrin/radixin/moesin (ERM) proteins are involved in actin filament/plasma membrane interaction that is regulated by Rho. We examined whether ERM proteins are directly phosphorylated by Rho- associated kinase (Rho-kinase), a direct target of Rho. Recombinant full-length and COOH-terminal half radixin were incubated with constitutively active catalytic domain of Rho-kinase, and ∼30 and ∼100% of these molecules, respectively, were phosphorylated mainly at the COOH-terminal threonine (T564). Next, to detect Rho-kinase–dependent phosphorylation of ERM proteins in vivo, we raised a mAb that recognized the T564-phosphorylated radixin as well as ezrin and moesin phosphorylated at the corresponding threonine residue (T567 and T558, respectively). Immunoblotting of serum-starved Swiss 3T3 cells with this mAb revealed that after LPA stimulation ERM proteins were rapidly phosphorylated at T567 (ezrin), T564 (radixin), and T558 (moesin) in a Rho-dependent manner and then dephosphorylated within 2 min. Furthermore, the T564 phosphorylation of recombinant COOH-terminal half radixin did not affect its ability to bind to actin filaments in vitro but significantly suppressed its direct interaction with the NH2-terminal half of radixin. These observations indicate that the Rho-kinase–dependent phosphorylation interferes with the intramolecular and/ or intermolecular head-to-tail association of ERM proteins, which is an important mechanism of regulation of their activity as actin filament/plasma membrane cross-linkers.

0 comments Cited 158 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II.

A P Somlyo (2000)

We here review mechanisms that can regulate the activity of myosin II, in smooth muscle and non-muscle cells, by modulating the Ca2+ sensitivity of myosin regulatory light chain (RLC) phosphorylation. The major mechanism of Ca2+ sensitization of smooth muscle contraction and non-muscle cell motility is through inhibition of the smooth muscle myosin phosphatase (MLCP) that dephosphorylates the RLC in smooth muscle and non-muscle. The active, GTP-bound form of the small GTPase RhoA activates a serine/threonine kinase, Rho-kinase, that phosphorylates the regulatory subunit of MLCP and inhibits phosphatase activity. G-protein-coupled release of arachidonic acid may also contribute to inhibition of MLCP acting, at least in part, through the Rho/Rho-kinase pathway. Protein kinase C(s) activated by phorbol esters and diacylglycerol can also inhibit MLCP by phosphorylating and thereby activating CPI-17, an inhibitor of its catalytic subunit; this mechanism is independent of the Rho/Rho-kinase pathway and plays only a minor, transient role in the G-protein-coupled mechanism of Ca2+ sensitization. Ca2+ sensitization by the Rho/Rho-kinase pathway contributes to the tonic phase of agonist-induced contraction in smooth muscle, and abnormally increased activation of myosin II by this mechanism is thought to play a role in diseases such as high blood pressure and cancer cell metastasis.

0 comments Cited 134 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Regulation of arterial diameter and wall [Ca2+] in cerebral arteries of rat by membrane potential and intravascular pressure.

Ken M. Nelson, J. Knot (1998)

1. The regulation of intracellular [Ca2+] in the smooth muscle cells in the wall of small pressurized cerebral arteries (100-200 micron) of rat was studied using simultaneous digital fluorescence video imaging of arterial diameter and wall [Ca2+], combined with microelectrode measurements of arterial membrane potential. 2. Elevation of intravascular pressure (from 10 to 100 mmHg) caused a membrane depolarization from -63 +/- 1 to -36 +/- 2 mV, increased arterial wall [Ca2+] from 119 +/- 10 to 245 +/- 9 nM, and constricted the arteries from 208 +/- 10 micron (fully dilated, Ca2+ free) to 116 +/- 7 micron or by 45 % ('myogenic tone'). 3. Pressure-induced increases in arterial wall [Ca2+] and vasoconstriction were blocked by inhibitors of voltage-dependent Ca2+ channels (diltiazem and nisoldipine) or to the same extent by removal of external Ca2+. 4. At a steady pressure (i.e. under isobaric conditions at 60 mmHg), the membrane potential was stable at -45 +/- 1 mV, intracellular [Ca2+] was 190 +/- 10 nM, and arteries were constricted by 41 % (to 115 +/- 7 micron from 196 +/- 8 micron fully dilated). Under this condition of -45 +/- 5 mV at 60 mmHg, the voltage sensitivity of wall [Ca2+] and diameter were 7.5 nM mV-1 and 7.5 micron mV-1, respectively, resulting in a Ca2+ sensitivity of diameter of 1 mum nM-1. 5. Membrane potential depolarization from -58 to -23 mV caused pressurized arteries (to 60 mmHg) to constrict over their entire working range, i.e. from maximally dilated to constricted. This depolarization was associated with an elevation of arterial wall [Ca2+] from 124 +/- 7 to 347 +/- 12 nM. These increases in arterial wall [Ca2+] and vasoconstriction were blocked by L-type voltage-dependent Ca2+ channel inhibitors. 6. The relationship between arterial wall [Ca2+] and membrane potential was not significantly different under isobaric (60 mmHg) and non-isobaric conditions (10-100 mmHg), suggesting that intravascular pressure regulates arterial wall [Ca2+] through changes in membrane potential. 7. The results are consistent with the idea that intravascular pressure causes membrane potential depolarization, which opens voltage-dependent Ca2+ channels, acting as 'voltage sensors', thus increasing Ca2+ entry and arterial wall [Ca2+], which leads to vasoconstriction.

0 comments Cited 102 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (publisher-id): JVR

Journal ID (nlm-ta): J Vasc Res

Journal ID (doi): 10.1159/issn.1018-1172

Title: Journal of Vascular Research

Publisher: S. Karger AG

ISSN (Print): 1018-1172

ISSN (Electronic): 1423-0135

Publication date Subscription-year: 2012

Publication date (Print): October 2012

Publication date (Electronic): 01 September 2012

Volume: 49

Issue: 6

Pages: 522-533

Affiliations

^aDepartment of Cellular Physiology, Institute of Neuroscience, and ^bDepartment of Pharmacology and Therapeutics, Institute of Experimental and Clinical Research, Université catholique de Louvain, Brussels, Belgium

Author notes

*Prof. Nicole Morel, Laboratoire de Physiologie Cellulaire, Université catholique de Louvain, Avenue Hippocrate 55 (B1-5512), BE–1200 Bruxelles (Belgium), Tel. +32 2 764 5549, E-Mail nicole.morel@uclouvain.be

Article

Publisher ID: 341230 Other ID: J Vasc Res 2012;49:522–533

DOI: 10.1159/000341230

PubMed ID: 22948674

SO-VID: 0e21f5c6-41d3-4792-b791-b251df730b16

License:

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

History

Date received : 13 April 2012

Date accepted : 10 June 2012

Page count

Figures: 7, Tables: 1, Pages: 12

Comments

Comment on this article

scite_

Cited by 2

See all cited by

Most referenced authors 283

See all reference authors

Different Effect of Rho Kinase Inhibition on Calcium Signaling in Rat Isolated Large and Small Arteries

Read this article at

Abstract

Related collections

Karger: Cardiovascular System

Most cited references 27

Rho-Kinase Phosphorylates COOH-terminal Threonines of Ezrin/Radixin/Moesin (ERM) Proteins and Regulates Their Head-to-Tail Association

Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II.

Regulation of arterial diameter and wall [Ca2+] in cerebral arteries of rat by membrane potential and intravascular pressure.

Author and article information

Journal

Affiliations

Author notes

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 226

Cited by 2

Most referenced authors 283