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ACE inhibition augments intracellular uptake of exogenous [ 125 I]‐Val 5 ‐angiotensin II in the Kidney of AT 1a receptor‐deficient mice
Author(s) -
Li Xiao Chun,
Shao Yuan,
Zhuo Jia Long
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1247-a
Subject(s) - angiotensin ii , endocrinology , captopril , medicine , chemistry , intracellular , renin–angiotensin system , kidney , receptor , blood pressure , biology , biochemistry
Intracellular uptake of angiotensin II (Ang II) is decreased in the kidneys of AT 1a receptor‐deficient mice (AT 1a ‐KO). This study determined whether this response is due to absence of AT 1a receptor‐mediated endocytosis or to increased local Ang II formation. Wild‐type (WT) and AT 1a ‐KO mice (n = 8) were treated with or without captopril (25 mg/kg/day, p.o.) for 2 weeks to suppress Ang II formation. Renal uptake of circulating Ang II was studied with infusion of [ 125 I]‐Val 5 ‐Ang II (250 pmol/min, i.v.) for 60 min. Basal blood pressure (SBP) was lower in AT 1a ‐KO (93 ± 2 mmHg) than in WT mice (118 ± 2 mmHg, p < 0.01). Captopril reduced SBP to similar extents in WT and AT 1a ‐KO mice (WT: 83 ± 4 mmHg vs. AT 1a ‐KO: 86 ± 2 mmHg, n.s.). Basal intracellular Ang II was lower in the kidneys of AT 1a ‐KO (68 ± 12 pg/100 mg KW) than WT mice (172 ± 25 pg/100 mg KW, p < 0.05), but plasma Ang II was higher in AT 1a ‐KO (377 ± 66 fmol/ml) than WT mice (105 ± 13 fmol/ml, p < 0.05). Intracellular uptake of [ 125 I]‐Val 5 ‐Ang II was lower in the kidneys of AT 1a ‐KO (5016 ±944 cpm/10 mg KW) than WT mice (18295 ± 2616 cpm/10 mg KW, p < 0.01). Captopril markedly decreased unlabeled plasma (WT: 40.3 ± 6.6 fmol/ml vs. AT 1a ‐KO: 147.9 ± 28.3 fmol/ml, p < 0.05) and intracellular Ang II in the kidneys (WT: 22.7 ± 8.5 pg/100 mg KW vs. AT 1a ‐KO: 7.6 ± 2.3 pg/100 mg KW, p < 0.05). By contrast, intracellular uptake of [ 125 I]‐Val 5 ‐Ang II was increased by 53% in the kidneys of WT mice and doubled in the kidneys of AT 1a ‐KO mice (p < 0.01). Our results support a predominant role of AT 1a receptors in mediating renal intracellular uptake of extracellular Ang II and suggest that extracellular Ang II also regulates the uptake. Supported by NIH Grant 5RO1DK067299.