Rho-kinase contributes to pressure-induced constriction of renal microvessels

Koichiro Honma, Koichi Hayashi, Shu Wakino, Hirobumi Tokuyama, Takeshi Kanda, Satoru Tatematsu, Kazuhiro Hasegawa, Seitaro Fujishima, Shingo Hori, Takao Saruta, Hiroshi Itoh

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Renal afferent arterioles (AFF) regulate glomerular capillary pressure through two main mechanisms: the myogenic response (MYO) and tubuloglomerular feedback (TGF). Because Rho-kinase and nitric oxide synthase (NOS) are established factors that modulate vascular tone, we examined the role of these factors in pressure-induced AFF tone in Wistar-Kyoto rats and in spontaneously hypertensive rats (SHR) using an intravital CCD camera. Elevated renal perfusion pressure elicited marked AFF constriction that was partially inhibited by gadolinium, furosemide and fasudil, which inhibit MYO, TGF and Rho-kinase, respectively; however, this AFF constriction was completely blocked by combined treatment with fasudil+gadolinium or fasudil+furosemide. S-methyl-l-thiocitrulline (SMTC) partially reversed the fasudil-induced inhibition of TGF-mediated, but not that of MYO-mediated, AFF constriction. In SHR, the pressure-induced AFF response was enhanced, and MYO- and TGF-induced constriction were exaggerated. In the presence of gadolinium, SMTC partially mitigated the fasudil-induced inhibition of TGF-mediated AFF constriction. Immunoblot analyses demonstrated that both Rho-kinase activity and neuronal NOS were augmented in SHR kidneys. In conclusion, Rho-kinase contributes to MYO- and TGF-mediated AFF responses, and these responses are enhanced in SHR. Furthermore, neuronal NOS-induced nitric oxide modulates the TGF mechanism. This mechanism constitutes a target for Rho-kinase in TGF-mediated AFF constriction.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalKeio Journal of Medicine
Volume63
Issue number1
DOIs
Publication statusPublished - 2014

Fingerprint

rho-Associated Kinases
Arterioles
Microvessels
Constriction
Kidney
Pressure
Inbred SHR Rats
Gadolinium
Nitric Oxide Synthase Type I
Furosemide
Inbred WKY Rats
Nitric Oxide Synthase
Nitric Oxide
Perfusion
fasudil

Keywords

  • Intravital CCD camera
  • Myogenic response
  • NNOS
  • Rho-kinase
  • Tubuloglomerular feedback

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Rho-kinase contributes to pressure-induced constriction of renal microvessels. / Honma, Koichiro; Hayashi, Koichi; Wakino, Shu; Tokuyama, Hirobumi; Kanda, Takeshi; Tatematsu, Satoru; Hasegawa, Kazuhiro; Fujishima, Seitaro; Hori, Shingo; Saruta, Takao; Itoh, Hiroshi.

In: Keio Journal of Medicine, Vol. 63, No. 1, 2014, p. 1-12.

Research output: Contribution to journalArticle

@article{618684dedb124bbdafb7fdf4ad15d534,
title = "Rho-kinase contributes to pressure-induced constriction of renal microvessels",
abstract = "Renal afferent arterioles (AFF) regulate glomerular capillary pressure through two main mechanisms: the myogenic response (MYO) and tubuloglomerular feedback (TGF). Because Rho-kinase and nitric oxide synthase (NOS) are established factors that modulate vascular tone, we examined the role of these factors in pressure-induced AFF tone in Wistar-Kyoto rats and in spontaneously hypertensive rats (SHR) using an intravital CCD camera. Elevated renal perfusion pressure elicited marked AFF constriction that was partially inhibited by gadolinium, furosemide and fasudil, which inhibit MYO, TGF and Rho-kinase, respectively; however, this AFF constriction was completely blocked by combined treatment with fasudil+gadolinium or fasudil+furosemide. S-methyl-l-thiocitrulline (SMTC) partially reversed the fasudil-induced inhibition of TGF-mediated, but not that of MYO-mediated, AFF constriction. In SHR, the pressure-induced AFF response was enhanced, and MYO- and TGF-induced constriction were exaggerated. In the presence of gadolinium, SMTC partially mitigated the fasudil-induced inhibition of TGF-mediated AFF constriction. Immunoblot analyses demonstrated that both Rho-kinase activity and neuronal NOS were augmented in SHR kidneys. In conclusion, Rho-kinase contributes to MYO- and TGF-mediated AFF responses, and these responses are enhanced in SHR. Furthermore, neuronal NOS-induced nitric oxide modulates the TGF mechanism. This mechanism constitutes a target for Rho-kinase in TGF-mediated AFF constriction.",
keywords = "Intravital CCD camera, Myogenic response, NNOS, Rho-kinase, Tubuloglomerular feedback",
author = "Koichiro Honma and Koichi Hayashi and Shu Wakino and Hirobumi Tokuyama and Takeshi Kanda and Satoru Tatematsu and Kazuhiro Hasegawa and Seitaro Fujishima and Shingo Hori and Takao Saruta and Hiroshi Itoh",
year = "2014",
doi = "10.2302/kjm.2013-0001-OA",
language = "English",
volume = "63",
pages = "1--12",
journal = "Keio Journal of Medicine",
issn = "0022-9717",
publisher = "Keio University School of Medicine",
number = "1",

}

TY - JOUR

T1 - Rho-kinase contributes to pressure-induced constriction of renal microvessels

AU - Honma, Koichiro

AU - Hayashi, Koichi

AU - Wakino, Shu

AU - Tokuyama, Hirobumi

AU - Kanda, Takeshi

AU - Tatematsu, Satoru

AU - Hasegawa, Kazuhiro

AU - Fujishima, Seitaro

AU - Hori, Shingo

AU - Saruta, Takao

AU - Itoh, Hiroshi

PY - 2014

Y1 - 2014

N2 - Renal afferent arterioles (AFF) regulate glomerular capillary pressure through two main mechanisms: the myogenic response (MYO) and tubuloglomerular feedback (TGF). Because Rho-kinase and nitric oxide synthase (NOS) are established factors that modulate vascular tone, we examined the role of these factors in pressure-induced AFF tone in Wistar-Kyoto rats and in spontaneously hypertensive rats (SHR) using an intravital CCD camera. Elevated renal perfusion pressure elicited marked AFF constriction that was partially inhibited by gadolinium, furosemide and fasudil, which inhibit MYO, TGF and Rho-kinase, respectively; however, this AFF constriction was completely blocked by combined treatment with fasudil+gadolinium or fasudil+furosemide. S-methyl-l-thiocitrulline (SMTC) partially reversed the fasudil-induced inhibition of TGF-mediated, but not that of MYO-mediated, AFF constriction. In SHR, the pressure-induced AFF response was enhanced, and MYO- and TGF-induced constriction were exaggerated. In the presence of gadolinium, SMTC partially mitigated the fasudil-induced inhibition of TGF-mediated AFF constriction. Immunoblot analyses demonstrated that both Rho-kinase activity and neuronal NOS were augmented in SHR kidneys. In conclusion, Rho-kinase contributes to MYO- and TGF-mediated AFF responses, and these responses are enhanced in SHR. Furthermore, neuronal NOS-induced nitric oxide modulates the TGF mechanism. This mechanism constitutes a target for Rho-kinase in TGF-mediated AFF constriction.

AB - Renal afferent arterioles (AFF) regulate glomerular capillary pressure through two main mechanisms: the myogenic response (MYO) and tubuloglomerular feedback (TGF). Because Rho-kinase and nitric oxide synthase (NOS) are established factors that modulate vascular tone, we examined the role of these factors in pressure-induced AFF tone in Wistar-Kyoto rats and in spontaneously hypertensive rats (SHR) using an intravital CCD camera. Elevated renal perfusion pressure elicited marked AFF constriction that was partially inhibited by gadolinium, furosemide and fasudil, which inhibit MYO, TGF and Rho-kinase, respectively; however, this AFF constriction was completely blocked by combined treatment with fasudil+gadolinium or fasudil+furosemide. S-methyl-l-thiocitrulline (SMTC) partially reversed the fasudil-induced inhibition of TGF-mediated, but not that of MYO-mediated, AFF constriction. In SHR, the pressure-induced AFF response was enhanced, and MYO- and TGF-induced constriction were exaggerated. In the presence of gadolinium, SMTC partially mitigated the fasudil-induced inhibition of TGF-mediated AFF constriction. Immunoblot analyses demonstrated that both Rho-kinase activity and neuronal NOS were augmented in SHR kidneys. In conclusion, Rho-kinase contributes to MYO- and TGF-mediated AFF responses, and these responses are enhanced in SHR. Furthermore, neuronal NOS-induced nitric oxide modulates the TGF mechanism. This mechanism constitutes a target for Rho-kinase in TGF-mediated AFF constriction.

KW - Intravital CCD camera

KW - Myogenic response

KW - NNOS

KW - Rho-kinase

KW - Tubuloglomerular feedback

UR - http://www.scopus.com/inward/record.url?scp=84897406815&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897406815&partnerID=8YFLogxK

U2 - 10.2302/kjm.2013-0001-OA

DO - 10.2302/kjm.2013-0001-OA

M3 - Article

VL - 63

SP - 1

EP - 12

JO - Keio Journal of Medicine

JF - Keio Journal of Medicine

SN - 0022-9717

IS - 1

ER -