Vessel- and vasoconstrictor-dependent role of Rho/Rho-kinase in renal microvascular tone

Akira Nakamura, Koichi Hayashi, Yuri Ozawa, Keiji Fujiwara, Ken Okubo, Takeshi Kanda, Shu Wakino, Takao Saruta

Research output: Contribution to journalArticle

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Abstract

We examined the role of Rho/Rho-kinase in renal afferent and efferent arteriolar tone induced by angiotensin (Ang) II, KCl and elevated renal arterial pressure (from 80 to 180 mm Hg), using isolated perfused rat hydronephrotic kidney. In the condition with no vasoconstrictor stimuli, Y-27632, a Rho-kinase inhibitor, dilated only afferent (from 11.6 ± 0.4 to 14.1 ± 0.5 μm) but not efferent arterioles (from 11.6 ± 0.2 to 12.6 ± 0.7 μm) at 10-5 mol/l. During renal vasoconstriction by Ang II, Y-27632 restored the afferent arteriolar constriction (141 ± 10% reversal at 10-5 mol/l), whereas the ability of Y-27632 to inhibit the Ang II-induced efferent arteriolar constriction was diminished (73 ± 7% reversal). A similar action was observed with fasudil, another Rho-kinase inhibitor. Furthermore, Y-27632 impaired myogenic afferent arteriolar constriction, with 117 ± 17% inhibition at 10-5 mol/l. The inhibition by Y-27632 of the myogenic vasoconstriction was almost the same as that of the Ang II-induced tone of this vessel type. However, Y-27632 had a modest effect on KCl-induced vasoconstriction of afferent arterioles. In conclusion, the present study demonstrates a predominant role of Rho/Rho-kinase in mediating the basal and Ang II-induced tone of afferent, but not efferent, arterioles. Furthermore, the role of Rho/Rho-kinase in afferent arteriolar constriction differs, with a substantial contribution to Ang II-induced and myogenic constriction but a minimal role in depolarization-induced constriction. Since Ang II-induced, KCl-induced and myogenic constriction of afferent arterioles require calcium entry through voltage-dependent calcium channels, the interaction between Rho/Rho-kinase and the calcium entry pathway may determine the afferent arteriolar tone induced by these stimuli.

Original languageEnglish
Pages (from-to)244-251
Number of pages8
JournalJournal of Vascular Research
Volume40
Issue number3
DOIs
Publication statusPublished - 2003

Fingerprint

rho-Associated Kinases
Vasoconstrictor Agents
Constriction
Angiotensin II
Kidney
Arterioles
Vasoconstriction
Calcium
Calcium Channels
Y 27632
Arterial Pressure

Keywords

  • Afferent arterioles
  • Angiotensin II
  • Efferent arterioles
  • KCl
  • Myogenic response
  • Renal microcirculation
  • Rho
  • Rho-kinase
  • Y-27632

ASJC Scopus subject areas

  • Physiology

Cite this

Vessel- and vasoconstrictor-dependent role of Rho/Rho-kinase in renal microvascular tone. / Nakamura, Akira; Hayashi, Koichi; Ozawa, Yuri; Fujiwara, Keiji; Okubo, Ken; Kanda, Takeshi; Wakino, Shu; Saruta, Takao.

In: Journal of Vascular Research, Vol. 40, No. 3, 2003, p. 244-251.

Research output: Contribution to journalArticle

Nakamura, Akira ; Hayashi, Koichi ; Ozawa, Yuri ; Fujiwara, Keiji ; Okubo, Ken ; Kanda, Takeshi ; Wakino, Shu ; Saruta, Takao. / Vessel- and vasoconstrictor-dependent role of Rho/Rho-kinase in renal microvascular tone. In: Journal of Vascular Research. 2003 ; Vol. 40, No. 3. pp. 244-251.
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AU - Nakamura, Akira

AU - Hayashi, Koichi

AU - Ozawa, Yuri

AU - Fujiwara, Keiji

AU - Okubo, Ken

AU - Kanda, Takeshi

AU - Wakino, Shu

AU - Saruta, Takao

PY - 2003

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N2 - We examined the role of Rho/Rho-kinase in renal afferent and efferent arteriolar tone induced by angiotensin (Ang) II, KCl and elevated renal arterial pressure (from 80 to 180 mm Hg), using isolated perfused rat hydronephrotic kidney. In the condition with no vasoconstrictor stimuli, Y-27632, a Rho-kinase inhibitor, dilated only afferent (from 11.6 ± 0.4 to 14.1 ± 0.5 μm) but not efferent arterioles (from 11.6 ± 0.2 to 12.6 ± 0.7 μm) at 10-5 mol/l. During renal vasoconstriction by Ang II, Y-27632 restored the afferent arteriolar constriction (141 ± 10% reversal at 10-5 mol/l), whereas the ability of Y-27632 to inhibit the Ang II-induced efferent arteriolar constriction was diminished (73 ± 7% reversal). A similar action was observed with fasudil, another Rho-kinase inhibitor. Furthermore, Y-27632 impaired myogenic afferent arteriolar constriction, with 117 ± 17% inhibition at 10-5 mol/l. The inhibition by Y-27632 of the myogenic vasoconstriction was almost the same as that of the Ang II-induced tone of this vessel type. However, Y-27632 had a modest effect on KCl-induced vasoconstriction of afferent arterioles. In conclusion, the present study demonstrates a predominant role of Rho/Rho-kinase in mediating the basal and Ang II-induced tone of afferent, but not efferent, arterioles. Furthermore, the role of Rho/Rho-kinase in afferent arteriolar constriction differs, with a substantial contribution to Ang II-induced and myogenic constriction but a minimal role in depolarization-induced constriction. Since Ang II-induced, KCl-induced and myogenic constriction of afferent arterioles require calcium entry through voltage-dependent calcium channels, the interaction between Rho/Rho-kinase and the calcium entry pathway may determine the afferent arteriolar tone induced by these stimuli.

AB - We examined the role of Rho/Rho-kinase in renal afferent and efferent arteriolar tone induced by angiotensin (Ang) II, KCl and elevated renal arterial pressure (from 80 to 180 mm Hg), using isolated perfused rat hydronephrotic kidney. In the condition with no vasoconstrictor stimuli, Y-27632, a Rho-kinase inhibitor, dilated only afferent (from 11.6 ± 0.4 to 14.1 ± 0.5 μm) but not efferent arterioles (from 11.6 ± 0.2 to 12.6 ± 0.7 μm) at 10-5 mol/l. During renal vasoconstriction by Ang II, Y-27632 restored the afferent arteriolar constriction (141 ± 10% reversal at 10-5 mol/l), whereas the ability of Y-27632 to inhibit the Ang II-induced efferent arteriolar constriction was diminished (73 ± 7% reversal). A similar action was observed with fasudil, another Rho-kinase inhibitor. Furthermore, Y-27632 impaired myogenic afferent arteriolar constriction, with 117 ± 17% inhibition at 10-5 mol/l. The inhibition by Y-27632 of the myogenic vasoconstriction was almost the same as that of the Ang II-induced tone of this vessel type. However, Y-27632 had a modest effect on KCl-induced vasoconstriction of afferent arterioles. In conclusion, the present study demonstrates a predominant role of Rho/Rho-kinase in mediating the basal and Ang II-induced tone of afferent, but not efferent, arterioles. Furthermore, the role of Rho/Rho-kinase in afferent arteriolar constriction differs, with a substantial contribution to Ang II-induced and myogenic constriction but a minimal role in depolarization-induced constriction. Since Ang II-induced, KCl-induced and myogenic constriction of afferent arterioles require calcium entry through voltage-dependent calcium channels, the interaction between Rho/Rho-kinase and the calcium entry pathway may determine the afferent arteriolar tone induced by these stimuli.

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