Key Points
- To determine whether intracellular uptake of angiotensin II in the kidneys and adrenal glands is primarily mediated by AT1a receptors and modulated by prevailing endogenous hormone levels.
- Wild-type (Agtr1a+/+) and AT1a knockout (Agtr1a-/-) mice (n = 6–9 per group) received 2-week pretreatment with vehicle, captopril (25 mg/kg/day), or losartan (10 mg/kg/day).
- Mice were infused with [125I]Val5-ANG II for 60 minutes, followed by vascular clearance and quantitative in vivo autoradiography to quantify intracellular uptake in renal and adrenal tissues.
- Agtr1a-/- mice exhibited 65% lower basal intracellular renal ANG II (P < 0.001), threefold higher plasma ANG II (P < 0.01), fourfold higher urinary [125I]Val5-ANG II excretion (P < 0.001), and ~80% reduced renal and adrenal intracellular [125I]Val5-ANG II uptake (P < 0.01) versus wild-type.
- Captopril reduced endogenous plasma and renal ANG II (P < 0.01) while increasing [125I]Val5-ANG II uptake in kidneys and adrenals in both genotypes (P < 0.01), whereas losartan largely abolished uptake across both groups.
Structured PICO
PPopulationWild-type (Agtr1a+/+) and type 1a angiotensin receptor (AT1a) receptor-deficient (Agtr1a-/-) mice (n = 6-9 each group)
IInterventionPretreatment with captopril (25 mg/kg/day) or losartan (10 mg/kg/day) for 2 weeks, followed by [125I]Val5-ANG II infusion for 60 min
CComparatorNo pretreatment (control)
OOutcomeIntracellular uptake of [125I]Val5-ANG II in the kidney and adrenal glands determined by quantitative in vivo autoradiographysurrogate
Approximately 80% of intracellular ANG II uptake in the kidney and adrenal glands is mediated by AT1a receptors, suggesting a physiological role for AT1a receptor-mediated uptake of extracellular ANG II.