Angiotensin converting enzyme-independent angiotensin II production by chymase is up-regulated in the ischemic kidney in renovascular hypertension

Javid Sadjadi, Gerald L. Kramer, Chun Hua Yu, M. Burress Welborn, Mark C. Chappell, J. Gregory Modrall

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background. Tissue angiotensin II (ANG II) levels are elevated in both kidneys in renovascular hypertension (RVH). It has been demonstrated previously that intrarenal ANG II is augmented by an angiotensin converting enzyme (ACE) dependent mechanism in the non-ischemic kidney, but the role of ACE-independent production of ANG II in the kidney by the enzyme chymase is unknown. This study tested the hypothesis that intrarenal chymase activity is up-regulated in RVH. Methods. A two-kidney, one-clip (2K1C) rat model was used to induce RVH (n = 6 rats/group). Regulation of intrarenal chymase activity by plasma ANG II was investigated using an ANG II-infusion model. At sacrifice 14 days post-operatively, steady-state ANG II levels in plasma and kidney were quantified by radioimmunoassay. ANG II production was quantified in kidney homogenates by incubating at 37°C for 60 min with enzyme substrate (200 μm ANG I) alone or substrate containing the chymase inhibitor chymostatin. ANG II was separated and quantitated by HPLC. Chymase activity was defined as the fraction of ANG II production inhibited by Chymostatin. Results. 2K1C and ANG II-infused rats developed significant hypertension, compared to control rats (P = 0.0001 and P = 0.001, respectively). Chymase-dependent ANG II production was increased in the ischemic kidney, but not the non-ischemic kidney, of 2K1C rats compared to control animals (*P < 0.05). Intrarenal chymase activity was unchanged by ANG II infusion (P = NS). Conclusions. Chymase activity is up-regulated in the ischemic kidney of 2K1C rats. Plasma ANG II does not appear to regulate intrarenal chymase activity, suggesting that ischemia per se up-regulates chymase activity in the kidney. ACE-independent ANG II production by chymase may provide a mechanism for augmenting intrarenal ANG II in the ischemic kidney in RVH.

Original languageEnglish (US)
Pages (from-to)65-69
Number of pages5
JournalJournal of Surgical Research
Volume127
Issue number2
DOIs
StatePublished - Aug 2005

Fingerprint

Chymases
Renovascular Hypertension
Peptidyl-Dipeptidase A
Angiotensin II
Kidney
Enzymes

Keywords

  • Angiotensin II
  • Chymase
  • Hypertension
  • Kidney
  • Renovascular

ASJC Scopus subject areas

  • Surgery

Cite this

Angiotensin converting enzyme-independent angiotensin II production by chymase is up-regulated in the ischemic kidney in renovascular hypertension. / Sadjadi, Javid; Kramer, Gerald L.; Yu, Chun Hua; Welborn, M. Burress; Chappell, Mark C.; Modrall, J. Gregory.

In: Journal of Surgical Research, Vol. 127, No. 2, 08.2005, p. 65-69.

Research output: Contribution to journalArticle

Sadjadi, Javid ; Kramer, Gerald L. ; Yu, Chun Hua ; Welborn, M. Burress ; Chappell, Mark C. ; Modrall, J. Gregory. / Angiotensin converting enzyme-independent angiotensin II production by chymase is up-regulated in the ischemic kidney in renovascular hypertension. In: Journal of Surgical Research. 2005 ; Vol. 127, No. 2. pp. 65-69.
@article{2e6c4f1558504ba5b768bed419b913ac,
title = "Angiotensin converting enzyme-independent angiotensin II production by chymase is up-regulated in the ischemic kidney in renovascular hypertension",
abstract = "Background. Tissue angiotensin II (ANG II) levels are elevated in both kidneys in renovascular hypertension (RVH). It has been demonstrated previously that intrarenal ANG II is augmented by an angiotensin converting enzyme (ACE) dependent mechanism in the non-ischemic kidney, but the role of ACE-independent production of ANG II in the kidney by the enzyme chymase is unknown. This study tested the hypothesis that intrarenal chymase activity is up-regulated in RVH. Methods. A two-kidney, one-clip (2K1C) rat model was used to induce RVH (n = 6 rats/group). Regulation of intrarenal chymase activity by plasma ANG II was investigated using an ANG II-infusion model. At sacrifice 14 days post-operatively, steady-state ANG II levels in plasma and kidney were quantified by radioimmunoassay. ANG II production was quantified in kidney homogenates by incubating at 37°C for 60 min with enzyme substrate (200 μm ANG I) alone or substrate containing the chymase inhibitor chymostatin. ANG II was separated and quantitated by HPLC. Chymase activity was defined as the fraction of ANG II production inhibited by Chymostatin. Results. 2K1C and ANG II-infused rats developed significant hypertension, compared to control rats (P = 0.0001 and P = 0.001, respectively). Chymase-dependent ANG II production was increased in the ischemic kidney, but not the non-ischemic kidney, of 2K1C rats compared to control animals (*P < 0.05). Intrarenal chymase activity was unchanged by ANG II infusion (P = NS). Conclusions. Chymase activity is up-regulated in the ischemic kidney of 2K1C rats. Plasma ANG II does not appear to regulate intrarenal chymase activity, suggesting that ischemia per se up-regulates chymase activity in the kidney. ACE-independent ANG II production by chymase may provide a mechanism for augmenting intrarenal ANG II in the ischemic kidney in RVH.",
keywords = "Angiotensin II, Chymase, Hypertension, Kidney, Renovascular",
author = "Javid Sadjadi and Kramer, {Gerald L.} and Yu, {Chun Hua} and Welborn, {M. Burress} and Chappell, {Mark C.} and Modrall, {J. Gregory}",
year = "2005",
month = "8",
doi = "10.1016/j.jss.2005.02.031",
language = "English (US)",
volume = "127",
pages = "65--69",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Angiotensin converting enzyme-independent angiotensin II production by chymase is up-regulated in the ischemic kidney in renovascular hypertension

AU - Sadjadi, Javid

AU - Kramer, Gerald L.

AU - Yu, Chun Hua

AU - Welborn, M. Burress

AU - Chappell, Mark C.

AU - Modrall, J. Gregory

PY - 2005/8

Y1 - 2005/8

N2 - Background. Tissue angiotensin II (ANG II) levels are elevated in both kidneys in renovascular hypertension (RVH). It has been demonstrated previously that intrarenal ANG II is augmented by an angiotensin converting enzyme (ACE) dependent mechanism in the non-ischemic kidney, but the role of ACE-independent production of ANG II in the kidney by the enzyme chymase is unknown. This study tested the hypothesis that intrarenal chymase activity is up-regulated in RVH. Methods. A two-kidney, one-clip (2K1C) rat model was used to induce RVH (n = 6 rats/group). Regulation of intrarenal chymase activity by plasma ANG II was investigated using an ANG II-infusion model. At sacrifice 14 days post-operatively, steady-state ANG II levels in plasma and kidney were quantified by radioimmunoassay. ANG II production was quantified in kidney homogenates by incubating at 37°C for 60 min with enzyme substrate (200 μm ANG I) alone or substrate containing the chymase inhibitor chymostatin. ANG II was separated and quantitated by HPLC. Chymase activity was defined as the fraction of ANG II production inhibited by Chymostatin. Results. 2K1C and ANG II-infused rats developed significant hypertension, compared to control rats (P = 0.0001 and P = 0.001, respectively). Chymase-dependent ANG II production was increased in the ischemic kidney, but not the non-ischemic kidney, of 2K1C rats compared to control animals (*P < 0.05). Intrarenal chymase activity was unchanged by ANG II infusion (P = NS). Conclusions. Chymase activity is up-regulated in the ischemic kidney of 2K1C rats. Plasma ANG II does not appear to regulate intrarenal chymase activity, suggesting that ischemia per se up-regulates chymase activity in the kidney. ACE-independent ANG II production by chymase may provide a mechanism for augmenting intrarenal ANG II in the ischemic kidney in RVH.

AB - Background. Tissue angiotensin II (ANG II) levels are elevated in both kidneys in renovascular hypertension (RVH). It has been demonstrated previously that intrarenal ANG II is augmented by an angiotensin converting enzyme (ACE) dependent mechanism in the non-ischemic kidney, but the role of ACE-independent production of ANG II in the kidney by the enzyme chymase is unknown. This study tested the hypothesis that intrarenal chymase activity is up-regulated in RVH. Methods. A two-kidney, one-clip (2K1C) rat model was used to induce RVH (n = 6 rats/group). Regulation of intrarenal chymase activity by plasma ANG II was investigated using an ANG II-infusion model. At sacrifice 14 days post-operatively, steady-state ANG II levels in plasma and kidney were quantified by radioimmunoassay. ANG II production was quantified in kidney homogenates by incubating at 37°C for 60 min with enzyme substrate (200 μm ANG I) alone or substrate containing the chymase inhibitor chymostatin. ANG II was separated and quantitated by HPLC. Chymase activity was defined as the fraction of ANG II production inhibited by Chymostatin. Results. 2K1C and ANG II-infused rats developed significant hypertension, compared to control rats (P = 0.0001 and P = 0.001, respectively). Chymase-dependent ANG II production was increased in the ischemic kidney, but not the non-ischemic kidney, of 2K1C rats compared to control animals (*P < 0.05). Intrarenal chymase activity was unchanged by ANG II infusion (P = NS). Conclusions. Chymase activity is up-regulated in the ischemic kidney of 2K1C rats. Plasma ANG II does not appear to regulate intrarenal chymase activity, suggesting that ischemia per se up-regulates chymase activity in the kidney. ACE-independent ANG II production by chymase may provide a mechanism for augmenting intrarenal ANG II in the ischemic kidney in RVH.

KW - Angiotensin II

KW - Chymase

KW - Hypertension

KW - Kidney

KW - Renovascular

UR - http://www.scopus.com/inward/record.url?scp=23144433099&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23144433099&partnerID=8YFLogxK

U2 - 10.1016/j.jss.2005.02.031

DO - 10.1016/j.jss.2005.02.031

M3 - Article

VL - 127

SP - 65

EP - 69

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

IS - 2

ER -