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EDITORIAL FOCUS

In vivo regulation of AT_1a receptor-mediated intracellular uptake of [¹²⁵I]Val⁵-ANG II in the kidneys and adrenals of AT_1a receptor-deficient mice

¹Laboratory of Receptor and Signal Transduction, Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Hospital, and ²Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan

Submitted 27 August 2007 ; accepted in final form 20 November 2007

Using type 1a angiotensin receptor (AT_1a) receptor-deficient (Agtr1a–/–) mice and in vivo autoradiography, we tested the hypothesis that intracellular uptake of ANG II in the kidney and adrenal glands is primarily mediated by AT_1a receptors and that the response is regulated by prevailing endogenous ANG II. After pretreatment of wild-type (Agtr1a+/+) and Agtr1a–/– mice (n = 6–9 each group) with or without captopril (25 mg·kg^–1·day^–1) or losartan (10 mg·kg^–1·day^–1) for 2 wk, [¹²⁵I]Val⁵-ANG II was infused for 60 min. Intracellular uptake of [¹²⁵I]Val⁵-ANG II was determined by quantitative in vivo autoradiography after washout of circulating [¹²⁵I]Val⁵-ANG II. Basal intracellular ANG II levels were 65% lower in the kidney (P < 0.001), but plasma ANG II levels were threefold higher, in Agtr1a–/– than wild-type mice (P < 0.01). Although plasma [¹²⁵I]Val⁵-ANG II levels were similar, urinary excretion of [¹²⁵I]Val⁵-ANG II was fourfold higher in Agtr1a–/– mice (P < 0.001). By contrast, intracellular [¹²⁵I]Val⁵-ANG II levels were 80% lower in the kidney and adrenal glands of Agtr1a–/– mice (P < 0.01). Captopril decreased endogenous plasma and renal ANG II levels (P < 0.01) but increased intracellular uptake of [¹²⁵I]Val⁵-ANG II in the kidney and adrenal glands of wild-type and Agtr1a–/– mice (P < 0.01). Losartan largely blocked renal and adrenal uptake of [¹²⁵I]Val⁵-ANG II in wild-type and Agtr1a–/– mice. Thus 80% of intracellular ANG II uptake in the kidney and adrenal glands is mediated by AT_1a receptors, whereas AT_1b receptor- and other non-receptor-mediated mechanisms account for 20% of the response. Our results suggest that AT_1a receptor-mediated uptake of extracellular ANG II may play a physiological role in the kidney and adrenal glands.

AT₁ receptor-mediated endocytosis; in vivo autoradiography; losartan

This article has been cited by other articles:

				J. L. Zhuo Intrarenal Perfusion and Angiotensin II Levels Regulate In Vivo Angiotensin II Type 1 Receptor Imaging in the Kidney Hypertension, June 1, 2008; 51(6): e52 - e52. [Full Text] [PDF]

				J. Xia and Z. Szabo Response to Intrarenal Perfusion and Angiotensin II Levels Regulate In Vivo Angiotensin II Type 1 Receptor Imaging in the Kidney Hypertension, June 1, 2008; 51(6): e53 - e53. [Full Text] [PDF]