Positron-emission tomography imaging of the angiotensin II subtype 1 receptor in swine renal artery stenosis

Jinsong Xia, Esen Seckin, Yan Xiang, Melin Vranesic, William B. Mathews, Kelvin Hong, David A. Bluemke, Lilach O Lerman, Zsolt Szabo

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The angiotensin II subtype 1 receptor (AT1R) has been linked to the development and progression of renovascular hypertension. In this study we applied a pig model of renovascular hypertension to investigate the AT1R in vivo with positron-emission tomography (PET) and in vitro with quantitative autoradiography. AT1R PET measurements were performed with the radioligand [C]KR31173 in 11 control pigs and in 13 pigs with hemodynamically significant renal artery stenosis; 4 were treated with lisinopril for 2 weeks before PET imaging. The radioligand impulse response function was calculated by deconvolution analysis of the renal time-activity curves. Radioligand binding was quantified by the 80-minute retention of the impulse response function. Median values and interquartile ranges were used to illustrate group statistics. Radioligand retention was significantly increased (P=0.044) in hypoperfused kidneys of untreated (0.225; range: 0.150 to 0.373) and lisinopril-treated (0.237; range:0.224 to 0.272) animals compared with controls (0.142; range:0.096 to 0.156). Increased binding of [C]KR31173 documented by PET in vivo was confirmed by in vitro autoradiography. Both in vivo and in vitro binding measurements showed that the effect of renal artery stenosis on the AT1R was not abolished by lisinopril treatment. These studies provide insight into kidney biology as the first in vivo/in vitro experimental evidence about AT1R regulation in response to reduced perfusion of the kidney. The findings support the concept of introducing AT1R PET as a diagnostic biomarker of renovascular disease.

Original languageEnglish (US)
Pages (from-to)466-473
Number of pages8
JournalHypertension
Volume51
Issue number2 PART 2
DOIs
StatePublished - Feb 2008

Fingerprint

Renal Artery Obstruction
Angiotensin II
Positron-Emission Tomography
Swine
Lisinopril
Kidney
Renovascular Hypertension
Autoradiography
Perfusion
Biomarkers
In Vitro Techniques

Keywords

  • Angiotensin AT receptor
  • Animal models
  • Positron-emission tomography
  • Renovascular hypertension
  • Swine

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Xia, J., Seckin, E., Xiang, Y., Vranesic, M., Mathews, W. B., Hong, K., ... Szabo, Z. (2008). Positron-emission tomography imaging of the angiotensin II subtype 1 receptor in swine renal artery stenosis. Hypertension, 51(2 PART 2), 466-473. https://doi.org/10.1161/HYPERTENSIONAHA.107.102715

Positron-emission tomography imaging of the angiotensin II subtype 1 receptor in swine renal artery stenosis. / Xia, Jinsong; Seckin, Esen; Xiang, Yan; Vranesic, Melin; Mathews, William B.; Hong, Kelvin; Bluemke, David A.; Lerman, Lilach O; Szabo, Zsolt.

In: Hypertension, Vol. 51, No. 2 PART 2, 02.2008, p. 466-473.

Research output: Contribution to journalArticle

Xia, J, Seckin, E, Xiang, Y, Vranesic, M, Mathews, WB, Hong, K, Bluemke, DA, Lerman, LO & Szabo, Z 2008, 'Positron-emission tomography imaging of the angiotensin II subtype 1 receptor in swine renal artery stenosis', Hypertension, vol. 51, no. 2 PART 2, pp. 466-473. https://doi.org/10.1161/HYPERTENSIONAHA.107.102715
Xia, Jinsong ; Seckin, Esen ; Xiang, Yan ; Vranesic, Melin ; Mathews, William B. ; Hong, Kelvin ; Bluemke, David A. ; Lerman, Lilach O ; Szabo, Zsolt. / Positron-emission tomography imaging of the angiotensin II subtype 1 receptor in swine renal artery stenosis. In: Hypertension. 2008 ; Vol. 51, No. 2 PART 2. pp. 466-473.
@article{8c21d2d608374ab1a795591235f71640,
title = "Positron-emission tomography imaging of the angiotensin II subtype 1 receptor in swine renal artery stenosis",
abstract = "The angiotensin II subtype 1 receptor (AT1R) has been linked to the development and progression of renovascular hypertension. In this study we applied a pig model of renovascular hypertension to investigate the AT1R in vivo with positron-emission tomography (PET) and in vitro with quantitative autoradiography. AT1R PET measurements were performed with the radioligand [C]KR31173 in 11 control pigs and in 13 pigs with hemodynamically significant renal artery stenosis; 4 were treated with lisinopril for 2 weeks before PET imaging. The radioligand impulse response function was calculated by deconvolution analysis of the renal time-activity curves. Radioligand binding was quantified by the 80-minute retention of the impulse response function. Median values and interquartile ranges were used to illustrate group statistics. Radioligand retention was significantly increased (P=0.044) in hypoperfused kidneys of untreated (0.225; range: 0.150 to 0.373) and lisinopril-treated (0.237; range:0.224 to 0.272) animals compared with controls (0.142; range:0.096 to 0.156). Increased binding of [C]KR31173 documented by PET in vivo was confirmed by in vitro autoradiography. Both in vivo and in vitro binding measurements showed that the effect of renal artery stenosis on the AT1R was not abolished by lisinopril treatment. These studies provide insight into kidney biology as the first in vivo/in vitro experimental evidence about AT1R regulation in response to reduced perfusion of the kidney. The findings support the concept of introducing AT1R PET as a diagnostic biomarker of renovascular disease.",
keywords = "Angiotensin AT receptor, Animal models, Positron-emission tomography, Renovascular hypertension, Swine",
author = "Jinsong Xia and Esen Seckin and Yan Xiang and Melin Vranesic and Mathews, {William B.} and Kelvin Hong and Bluemke, {David A.} and Lerman, {Lilach O} and Zsolt Szabo",
year = "2008",
month = "2",
doi = "10.1161/HYPERTENSIONAHA.107.102715",
language = "English (US)",
volume = "51",
pages = "466--473",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "2 PART 2",

}

TY - JOUR

T1 - Positron-emission tomography imaging of the angiotensin II subtype 1 receptor in swine renal artery stenosis

AU - Xia, Jinsong

AU - Seckin, Esen

AU - Xiang, Yan

AU - Vranesic, Melin

AU - Mathews, William B.

AU - Hong, Kelvin

AU - Bluemke, David A.

AU - Lerman, Lilach O

AU - Szabo, Zsolt

PY - 2008/2

Y1 - 2008/2

N2 - The angiotensin II subtype 1 receptor (AT1R) has been linked to the development and progression of renovascular hypertension. In this study we applied a pig model of renovascular hypertension to investigate the AT1R in vivo with positron-emission tomography (PET) and in vitro with quantitative autoradiography. AT1R PET measurements were performed with the radioligand [C]KR31173 in 11 control pigs and in 13 pigs with hemodynamically significant renal artery stenosis; 4 were treated with lisinopril for 2 weeks before PET imaging. The radioligand impulse response function was calculated by deconvolution analysis of the renal time-activity curves. Radioligand binding was quantified by the 80-minute retention of the impulse response function. Median values and interquartile ranges were used to illustrate group statistics. Radioligand retention was significantly increased (P=0.044) in hypoperfused kidneys of untreated (0.225; range: 0.150 to 0.373) and lisinopril-treated (0.237; range:0.224 to 0.272) animals compared with controls (0.142; range:0.096 to 0.156). Increased binding of [C]KR31173 documented by PET in vivo was confirmed by in vitro autoradiography. Both in vivo and in vitro binding measurements showed that the effect of renal artery stenosis on the AT1R was not abolished by lisinopril treatment. These studies provide insight into kidney biology as the first in vivo/in vitro experimental evidence about AT1R regulation in response to reduced perfusion of the kidney. The findings support the concept of introducing AT1R PET as a diagnostic biomarker of renovascular disease.

AB - The angiotensin II subtype 1 receptor (AT1R) has been linked to the development and progression of renovascular hypertension. In this study we applied a pig model of renovascular hypertension to investigate the AT1R in vivo with positron-emission tomography (PET) and in vitro with quantitative autoradiography. AT1R PET measurements were performed with the radioligand [C]KR31173 in 11 control pigs and in 13 pigs with hemodynamically significant renal artery stenosis; 4 were treated with lisinopril for 2 weeks before PET imaging. The radioligand impulse response function was calculated by deconvolution analysis of the renal time-activity curves. Radioligand binding was quantified by the 80-minute retention of the impulse response function. Median values and interquartile ranges were used to illustrate group statistics. Radioligand retention was significantly increased (P=0.044) in hypoperfused kidneys of untreated (0.225; range: 0.150 to 0.373) and lisinopril-treated (0.237; range:0.224 to 0.272) animals compared with controls (0.142; range:0.096 to 0.156). Increased binding of [C]KR31173 documented by PET in vivo was confirmed by in vitro autoradiography. Both in vivo and in vitro binding measurements showed that the effect of renal artery stenosis on the AT1R was not abolished by lisinopril treatment. These studies provide insight into kidney biology as the first in vivo/in vitro experimental evidence about AT1R regulation in response to reduced perfusion of the kidney. The findings support the concept of introducing AT1R PET as a diagnostic biomarker of renovascular disease.

KW - Angiotensin AT receptor

KW - Animal models

KW - Positron-emission tomography

KW - Renovascular hypertension

KW - Swine

UR - http://www.scopus.com/inward/record.url?scp=38549133436&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38549133436&partnerID=8YFLogxK

U2 - 10.1161/HYPERTENSIONAHA.107.102715

DO - 10.1161/HYPERTENSIONAHA.107.102715

M3 - Article

C2 - 18172054

AN - SCOPUS:38549133436

VL - 51

SP - 466

EP - 473

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 2 PART 2

ER -