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(Hypertension. 2008;51:466.)
© 2008 American Heart Association, Inc.

Original Articles Part 2

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

From the Departments of Radiology (J.X., E.S., M.V., W.B.M., K.H., D.A.B., Z.S.) and Physiology (Y.X.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Medicine (L.O.L.), Mayo Clinic College of Medicine, Rochester, Minn.

Correspondence to Zsolt Szabo, Johns Hopkins Outpatient Center, Room JHOC 3233, 601 N Caroline St, Baltimore, MD 21287-0817. E-mail zszabo{at}jhmi.edu

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 [¹¹C]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 [¹¹C]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.

Key Words: positron-emission tomography • angiotensin AT₁ receptor • swine • animal models • renovascular hypertension

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