RhoA/Rho kinase and nitric oxide modulate the agonist-induced pulmonary artery diameter response time

Christa Boer, Peter J.W. Van Der Linden, Gert Jan Scheffer, Nico Westerhof, Jaap J. De Lange, Pieter Sipkema

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

We studied the amplitude and response time (RT; time to 50% of maximal response) of pulmonary vasoreactivity and investigated whether the characteristics of pulmonary vasoreactivity could be modulated by endothelium removal, nitric oxide (NO) synthase inhibition [N G-nitro-Larginine (L-NNA)], RhoA activation [lysophosphatidic acid (LPA)] and Rho kinase inhibition (Y-27632). Slow acetylcholine-induced pulmonary vasodilation (262 ± 5 s) was not due to the RT of endothelial NO release (45-55 s) and was always longer than RT in renal arteries (15 ± 4 s). The rate-determining step is located in the smooth muscle cells. This was confirmed by the existing differences between the RT of the NO solution and KCl-induced renal and pulmonary vasoreactivity in endothelium-denuded arteries. We found that the pulmonary contractile amplitude increases and the RT decreases by L-NNA or LPA. In contrast, Y-27632 reduced the contractile amplitude and increased the RT in pulmonary arteries. These phenomena were dependent on the contractile stimulus (phenylephrine or KCl). In conclusion, slow pulmonary vasoreactivity is a smooth muscle cell characteristic that can be enhanced by RhoA and NO or endothelium removal. These effects were counteracted by Rho kinase inhibition. We show a role for RhoA/Rho kinase and NO in the modulation of pulmonary vascular reactivity.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume282
Issue number3 51-3
Publication statusPublished - 29 Jun 2002

Cite this

@article{b2f45d04832f42018cc6c127f23ada73,
title = "RhoA/Rho kinase and nitric oxide modulate the agonist-induced pulmonary artery diameter response time",
abstract = "We studied the amplitude and response time (RT; time to 50{\%} of maximal response) of pulmonary vasoreactivity and investigated whether the characteristics of pulmonary vasoreactivity could be modulated by endothelium removal, nitric oxide (NO) synthase inhibition [N G-nitro-Larginine (L-NNA)], RhoA activation [lysophosphatidic acid (LPA)] and Rho kinase inhibition (Y-27632). Slow acetylcholine-induced pulmonary vasodilation (262 ± 5 s) was not due to the RT of endothelial NO release (45-55 s) and was always longer than RT in renal arteries (15 ± 4 s). The rate-determining step is located in the smooth muscle cells. This was confirmed by the existing differences between the RT of the NO solution and KCl-induced renal and pulmonary vasoreactivity in endothelium-denuded arteries. We found that the pulmonary contractile amplitude increases and the RT decreases by L-NNA or LPA. In contrast, Y-27632 reduced the contractile amplitude and increased the RT in pulmonary arteries. These phenomena were dependent on the contractile stimulus (phenylephrine or KCl). In conclusion, slow pulmonary vasoreactivity is a smooth muscle cell characteristic that can be enhanced by RhoA and NO or endothelium removal. These effects were counteracted by Rho kinase inhibition. We show a role for RhoA/Rho kinase and NO in the modulation of pulmonary vascular reactivity.",
keywords = "Amplitude of constriction, Endothelium, Nitric oxide electrode, Response time",
author = "Christa Boer and {Van Der Linden}, {Peter J.W.} and Scheffer, {Gert Jan} and Nico Westerhof and {De Lange}, {Jaap J.} and Pieter Sipkema",
year = "2002",
month = "6",
day = "29",
language = "English",
volume = "282",
journal = "American Journal of Physiology. Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "3 51-3",

}

RhoA/Rho kinase and nitric oxide modulate the agonist-induced pulmonary artery diameter response time. / Boer, Christa; Van Der Linden, Peter J.W.; Scheffer, Gert Jan; Westerhof, Nico; De Lange, Jaap J.; Sipkema, Pieter.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 282, No. 3 51-3, 29.06.2002.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - RhoA/Rho kinase and nitric oxide modulate the agonist-induced pulmonary artery diameter response time

AU - Boer, Christa

AU - Van Der Linden, Peter J.W.

AU - Scheffer, Gert Jan

AU - Westerhof, Nico

AU - De Lange, Jaap J.

AU - Sipkema, Pieter

PY - 2002/6/29

Y1 - 2002/6/29

N2 - We studied the amplitude and response time (RT; time to 50% of maximal response) of pulmonary vasoreactivity and investigated whether the characteristics of pulmonary vasoreactivity could be modulated by endothelium removal, nitric oxide (NO) synthase inhibition [N G-nitro-Larginine (L-NNA)], RhoA activation [lysophosphatidic acid (LPA)] and Rho kinase inhibition (Y-27632). Slow acetylcholine-induced pulmonary vasodilation (262 ± 5 s) was not due to the RT of endothelial NO release (45-55 s) and was always longer than RT in renal arteries (15 ± 4 s). The rate-determining step is located in the smooth muscle cells. This was confirmed by the existing differences between the RT of the NO solution and KCl-induced renal and pulmonary vasoreactivity in endothelium-denuded arteries. We found that the pulmonary contractile amplitude increases and the RT decreases by L-NNA or LPA. In contrast, Y-27632 reduced the contractile amplitude and increased the RT in pulmonary arteries. These phenomena were dependent on the contractile stimulus (phenylephrine or KCl). In conclusion, slow pulmonary vasoreactivity is a smooth muscle cell characteristic that can be enhanced by RhoA and NO or endothelium removal. These effects were counteracted by Rho kinase inhibition. We show a role for RhoA/Rho kinase and NO in the modulation of pulmonary vascular reactivity.

AB - We studied the amplitude and response time (RT; time to 50% of maximal response) of pulmonary vasoreactivity and investigated whether the characteristics of pulmonary vasoreactivity could be modulated by endothelium removal, nitric oxide (NO) synthase inhibition [N G-nitro-Larginine (L-NNA)], RhoA activation [lysophosphatidic acid (LPA)] and Rho kinase inhibition (Y-27632). Slow acetylcholine-induced pulmonary vasodilation (262 ± 5 s) was not due to the RT of endothelial NO release (45-55 s) and was always longer than RT in renal arteries (15 ± 4 s). The rate-determining step is located in the smooth muscle cells. This was confirmed by the existing differences between the RT of the NO solution and KCl-induced renal and pulmonary vasoreactivity in endothelium-denuded arteries. We found that the pulmonary contractile amplitude increases and the RT decreases by L-NNA or LPA. In contrast, Y-27632 reduced the contractile amplitude and increased the RT in pulmonary arteries. These phenomena were dependent on the contractile stimulus (phenylephrine or KCl). In conclusion, slow pulmonary vasoreactivity is a smooth muscle cell characteristic that can be enhanced by RhoA and NO or endothelium removal. These effects were counteracted by Rho kinase inhibition. We show a role for RhoA/Rho kinase and NO in the modulation of pulmonary vascular reactivity.

KW - Amplitude of constriction

KW - Endothelium

KW - Nitric oxide electrode

KW - Response time

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JO - American Journal of Physiology. Heart and Circulatory Physiology

JF - American Journal of Physiology. Heart and Circulatory Physiology

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IS - 3 51-3

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