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In Vivo Investigation of Estrogen Regulation of Adrenal and Renal Angiotensin (AT1) Receptor Expression by PET

Taofeek K. Owonikoko, MD1, Maria E. Fabucci, MD2, Philip R. Brown, PhD3, Nighat Nisar, MD1, John Hilton, PhD1, William B. Mathews, PhD1, Hayden T. Ravert, PhD1, Paige Rauseo1, Kathryn Sandberg, PhD2, Robert F. Dannals, PhD1 and Zsolt Szabo, MD, PhD1

1 Division of Nuclear Medicine, Johns Hopkins University, Baltimore, Maryland
2 Division of Nephrology and Hypertension, Georgetown University, Washington, DC
3 Division of Comparative Medicine, Johns Hopkins University, Baltimore, Maryland



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FIGURE 1. Accumulation of 11C-L-159,884 in kidney and adrenal 55–95 min after injection (left image) and ROIs of left kidney and left adrenal gland (right image). ROIs were defined on all image slices showing organs. ROI of kidney included only renal cortex (C), whereas ROI of adrenal included entire gland (A).

 


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FIGURE 2. Effect of estrogen depletion on cAT1 receptor expression in renal cortex as determined by PET imaging in vivo. (A) Ki changes in individual animals first off and then on E2 (off-on model) and in animals first on and then off E2 (on-off model). (B) Ki in 2 groups of animals (off-on and on-off model) and in all pooled animals off and on E2. Differences between off and on E2 were consistent but statistically not significant in separate off-on and on-off subgroups. Differences between pooled parameters were statistically significant (P = 0.021).

 


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FIGURE 3. Effect of estrogen depletion on cAT1 receptor expression in adrenal gland as determined by PET imaging in vivo. (A) Ki changes in individual animals first off and then on E2 (off-on model) and in animals first on and then off E2 (on-off model). (B) Ki in 2 groups of animals (off-on and on-off model) and in all pooled animals off and on E2. As in kidney (Fig. 2), differences between off and on E2 were consistent but statistically not significant in separate off-on and on-off subgroups. Differences between pooled parameters were statistically significant (P = 0.003).

 


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FIGURE 4. Effect of estrogen on cAT1 receptor expression as measured by in vitro radioligand binding expressed as Bmax in units of fmol/mg protein. Differences were significant in both glomerular (A) (P = 0.002) and adrenal (B) (P = 0.012) Bmax.

 





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