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Nitric oxide relaxes rat tail artery smooth muscle by cyclic GMP-independent decrease in calcium sensitivity of myofilaments

Soloviev, A; Lehen'kyi, V; Zelensky, S and Hellstrand, Per LU (2004) In Cell Calcium 36(2). p.165-173
Abstract
The effects of authentic nitric oxide (NO, 10(-6) M) and NO-donors such as sodium nitroprusside (SNP, 10(-5) M) and glyceryl trinitrate (GTN, 10(-4) M) on contractile force and free intracellular calcium level ([Ca2+],) were studied on precontracted with high potassium chloride (KCI, 70 mM) isolated rings of rat tail artery. The sensitivity of contractile myofilaments to Ca2+ was measured using chemically permeabilized (alpha-toxin, beta-escin, Triton X-100) vascular rings. [Ca2+](i) and contractile activity were measured simultaneously. The relationship of [Ca2+](i) and tension developed was studied in endothelium-denuded rings and controlled calcium response was evaluated in both endothelium-denuded and permeabilized vascular rings. Both... (More)
The effects of authentic nitric oxide (NO, 10(-6) M) and NO-donors such as sodium nitroprusside (SNP, 10(-5) M) and glyceryl trinitrate (GTN, 10(-4) M) on contractile force and free intracellular calcium level ([Ca2+],) were studied on precontracted with high potassium chloride (KCI, 70 mM) isolated rings of rat tail artery. The sensitivity of contractile myofilaments to Ca2+ was measured using chemically permeabilized (alpha-toxin, beta-escin, Triton X-100) vascular rings. [Ca2+](i) and contractile activity were measured simultaneously. The relationship of [Ca2+](i) and tension developed was studied in endothelium-denuded rings and controlled calcium response was evaluated in both endothelium-denuded and permeabilized vascular rings. Both authentic NO and NO-donors decreased [Ca2+](i) and high potassium-induced tension with a different time course. Inhibitor of soluble guanylyl cyclase (sGC) LY83583 (10(-5) M) did not affect SNP-induced relaxation whereas the other sGC inhibitor ODQ (10(-6) M) attenuated SNP-induced relaxation. Both inhibitors had no effect on NO- and SNP-induced reduction in [Ca2+](i). On the contrary, GTN induced neither relaxation nor decrease in [Ca2+](i) on application of both LY83583 and ODQ. Tail artery rings permeabilized with alpha-toxin, beta-escin, but not with Triton X-100 were relaxed by authentic NO and NO-donors, but to a less extent than non-permeabilized rings. Dithioerythritol (DTE, 5 x 10(-3) M) that maintains sulfhydryl (SH) groups in reduced state preventing their nitrosylation attenuated NO-induced relaxation in both non-permeabilized and permeabilized tail artery rings. The cyclic heptapeptide mycrocystin-LR (MC-LR) (10(-5) M), an inhibitor of type I and 2A phosphatases, induced sustained increase in tension of beta-escin permeabilized rings in low Ca2+ (10(-8) M) solution. The tension was not affected by authentic NO and SNP. We conclude that authentic NO and SNP relax rat tail artery smooth muscle (SM) in the presence of inhibitors of sGC via cyclic guanosine monophosphate (cGMP)- independent pathway, whereas relaxation induced by GTN is inhibited. The data demonstrate that cGMP-dependent pathway in vascular smooth muscle is ubiquitous, but not the only way of relaxation induced by NO. NO can modulate vascular tone directly by reducing sensitivity of contractile myofilaments to [Ca2+](i) and may involve activation of protein phosphatase(s). (C) 2004 Elsevier Ltd. All rights reserved. (Less)
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organization
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Contribution to journal
publication status
published
subject
keywords
intracellular free calcium level, monophosphate, cyclic guanosine, soluble guanylyl cyclase, nitric oxide, NO-donors, myofilament calcium, sensitivity
in
Cell Calcium
volume
36
issue
2
pages
165 - 173
publisher
Elsevier
external identifiers
  • wos:000222770700008
  • pmid:15193864
  • scopus:3242666332
ISSN
0143-4160
DOI
10.1016/j.ceca.2004.02.002
language
English
LU publication?
yes
id
4c105be4-6993-4d82-a8e2-5c7a243e2720 (old id 272551)
date added to LUP
2007-11-02 08:26:00
date last changed
2017-04-23 04:30:17
@article{4c105be4-6993-4d82-a8e2-5c7a243e2720,
  abstract     = {The effects of authentic nitric oxide (NO, 10(-6) M) and NO-donors such as sodium nitroprusside (SNP, 10(-5) M) and glyceryl trinitrate (GTN, 10(-4) M) on contractile force and free intracellular calcium level ([Ca2+],) were studied on precontracted with high potassium chloride (KCI, 70 mM) isolated rings of rat tail artery. The sensitivity of contractile myofilaments to Ca2+ was measured using chemically permeabilized (alpha-toxin, beta-escin, Triton X-100) vascular rings. [Ca2+](i) and contractile activity were measured simultaneously. The relationship of [Ca2+](i) and tension developed was studied in endothelium-denuded rings and controlled calcium response was evaluated in both endothelium-denuded and permeabilized vascular rings. Both authentic NO and NO-donors decreased [Ca2+](i) and high potassium-induced tension with a different time course. Inhibitor of soluble guanylyl cyclase (sGC) LY83583 (10(-5) M) did not affect SNP-induced relaxation whereas the other sGC inhibitor ODQ (10(-6) M) attenuated SNP-induced relaxation. Both inhibitors had no effect on NO- and SNP-induced reduction in [Ca2+](i). On the contrary, GTN induced neither relaxation nor decrease in [Ca2+](i) on application of both LY83583 and ODQ. Tail artery rings permeabilized with alpha-toxin, beta-escin, but not with Triton X-100 were relaxed by authentic NO and NO-donors, but to a less extent than non-permeabilized rings. Dithioerythritol (DTE, 5 x 10(-3) M) that maintains sulfhydryl (SH) groups in reduced state preventing their nitrosylation attenuated NO-induced relaxation in both non-permeabilized and permeabilized tail artery rings. The cyclic heptapeptide mycrocystin-LR (MC-LR) (10(-5) M), an inhibitor of type I and 2A phosphatases, induced sustained increase in tension of beta-escin permeabilized rings in low Ca2+ (10(-8) M) solution. The tension was not affected by authentic NO and SNP. We conclude that authentic NO and SNP relax rat tail artery smooth muscle (SM) in the presence of inhibitors of sGC via cyclic guanosine monophosphate (cGMP)- independent pathway, whereas relaxation induced by GTN is inhibited. The data demonstrate that cGMP-dependent pathway in vascular smooth muscle is ubiquitous, but not the only way of relaxation induced by NO. NO can modulate vascular tone directly by reducing sensitivity of contractile myofilaments to [Ca2+](i) and may involve activation of protein phosphatase(s). (C) 2004 Elsevier Ltd. All rights reserved.},
  author       = {Soloviev, A and Lehen'kyi, V and Zelensky, S and Hellstrand, Per},
  issn         = {0143-4160},
  keyword      = {intracellular free calcium level,monophosphate,cyclic guanosine,soluble guanylyl cyclase,nitric oxide,NO-donors,myofilament calcium,sensitivity},
  language     = {eng},
  number       = {2},
  pages        = {165--173},
  publisher    = {Elsevier},
  series       = {Cell Calcium},
  title        = {Nitric oxide relaxes rat tail artery smooth muscle by cyclic GMP-independent decrease in calcium sensitivity of myofilaments},
  url          = {http://dx.doi.org/10.1016/j.ceca.2004.02.002},
  volume       = {36},
  year         = {2004},
}