title: Positron-emission tomography imaging of the angiotensin II subtype 1 receptor in swine renal artery stenosis.
abstract: The angiotensin II subtype 1 receptor (AT(1)R) 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 AT(1)R in vivo with positron-emission tomography (PET) and in vitro with quantitative autoradiography. AT(1)R PET measurements were performed with the radioligand [(11)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 [(11)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 AT(1)R was not abolished by lisinopril treatment. These studies provide insight into kidney biology as the first in vivo/in vitro experimental evidence about AT(1)R regulation in response to reduced perfusion of the kidney. The findings support the concept of introducing AT(1)R PET as a diagnostic biomarker of renovascular disease.
authors.affiliation: Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Xia
authors.forename: Esen
authors.initials: E
authors.lastname: Seckin
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiang
authors.forename: Melin
authors.initials: M
authors.lastname: Vranesic
authors.forename: William B
authors.initials: WB
authors.lastname: Mathews
authors.forename: Kelvin
authors.initials: K
authors.lastname: Hong
authors.forename: David A
authors.initials: DA
authors.lastname: Bluemke
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szabo
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001345:Autoradiography; D002250:Carbon Radioisotopes; D007093:Imidazoles / Q000378:metabolism; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism; D017706:Lisinopril / Q000494:pharmacology; D018810:Magnetic Resonance Angiography; D049268:Positron-Emission Tomography; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D012078:Renal Artery Obstruction / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D013552:Swine; D013777:Tetrazoles / Q000378:metabolism
chemical_list: C493912:2-butyl-5-methoxymethyl-6-(1-oxopyridin-2-yl)-3-((2'-(1H-tetrazol-5-yl)bipohenyl-4-yl)methyl)-3H-imidazo(4,5-b)pyridine; D000959:Antihypertensive Agents; D002250:Carbon Radioisotopes; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D017706:Lisinopril