Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2004
In vivo investigation of estrogen regulation of adrenal and renal angiotensin (AT1) receptor expression by PET.
Сравнительное исследованиеСтатьяПоддержка службы здравоохранения СШАНазвание и аннотация: Перевод в очереди
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Owonikoko Taofeek K, Fabucci Maria E, Brown Philip R, Nisar Nighat, Hilton John, Mathews William B, Ravert Hayden T, Rauseo Paige, Sandberg Kathryn, Dannals Robert F, Szabo Zsolt
Аннотация
UNLABELLED: The renin angiotensin system (RAS) has been implicated as one mediator of the cardiovascular effects of estrogen. Since changes in angiotensin type 1 (AT(1)) receptor expression are central to modulation of the RAS, we used the noninvasive PET imaging technique to study for the in vivo effects of estrogen on membrane and intracellular AT(1) receptors.
METHODS: Dynamic PET measurements of canine AT(1) (cAT(1)) receptors using the radiolabeled AT(1) receptor antagonist, (11)C-L-159,884, were performed during 2-wk consecutive periods of estrogen deprivation induced by ovariectomy and 17beta-estradiol (E(2)) replacement.
RESULTS: Kinetic modeling of time-activity curves in the kidney and adrenal showed lower receptor expression in the estrogen replete state (21% and 30% decrease in Gjedde-Patlak slope, influx constant, respectively). These in vivo findings correlated with in vitro radioligand-binding assays with (125)I-[Sar(1),Ile(8)]angiotensin II showing reduced AT(1) receptor number in the adrenal (35%), glomeruli (30%), myocardium (35%), and liver (21%) in the estrogen-replenished compared with estrogen-depleted animals.
CONCLUSION: Although other endogenous systems are known to regulate AT(1) receptors and could compete with estrogenic actions, these PET studies reveal that estrogen attenuates AT(1) receptor expression in vivo. Thus, estrogen modulation of AT(1) receptors may contribute to the cardiovascular protective effects associated with estrogen.
METHODS: Dynamic PET measurements of canine AT(1) (cAT(1)) receptors using the radiolabeled AT(1) receptor antagonist, (11)C-L-159,884, were performed during 2-wk consecutive periods of estrogen deprivation induced by ovariectomy and 17beta-estradiol (E(2)) replacement.
RESULTS: Kinetic modeling of time-activity curves in the kidney and adrenal showed lower receptor expression in the estrogen replete state (21% and 30% decrease in Gjedde-Patlak slope, influx constant, respectively). These in vivo findings correlated with in vitro radioligand-binding assays with (125)I-[Sar(1),Ile(8)]angiotensin II showing reduced AT(1) receptor number in the adrenal (35%), glomeruli (30%), myocardium (35%), and liver (21%) in the estrogen-replenished compared with estrogen-depleted animals.
CONCLUSION: Although other endogenous systems are known to regulate AT(1) receptors and could compete with estrogenic actions, these PET studies reveal that estrogen attenuates AT(1) receptor expression in vivo. Thus, estrogen modulation of AT(1) receptors may contribute to the cardiovascular protective effects associated with estrogen.