Atrap deficiency increases arterial blood pressure and plasma volume.
The angiotensin receptor-associated protein (Atrap) interacts with angiotensin II (AngII) type 1 (AT1) receptors and facilitates their internalization in vitro, but little is known about the function of Atrap in vivo. Here, we detected Atrap expression in several organs of wild-type mice; the highest expression was in the kidney where it localized to the proximal tubule, particularly the brush border. There was no Atrap expression in the renal vasculature or juxtaglomerular cells. We generated Atrap-deficient (Atrap-/-) mice, which were viable and seemed grossly normal. Mean systolic BP was significantly higher in Atrap-/- mice compared with wild-type mice. Dose-response relationships of arterial BP after acute AngII infusion were similar in both genotypes. Plasma volume was significantly higher and plasma renin concentration was markedly lower in Atrap-/- mice compared with wild-type mice. (125)I-AngII binding showed enhanced surface expression of AT1 receptors in the renal cortex of Atrap-/- mice, accompanied by increased carboanhydrase-sensitive proximal tubular function. In summary, Atrap-/- mice have increased arterial pressure and plasma volume. Atrap seems to modulate volume status by acting as a negative regulator of AT1 receptors in the renal tubules.
Oppermann
Mona
M
Children's Hospital, University Medical Center, Germany.
Gess
Bernhard
B
Schweda
Frank
F
Castrop
Hayo
H
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006977:Hypertension, Renal / Q000235:genetics* / Q000503:physiopathology; D007457:Iodine Radioisotopes; D007545:Isoproterenol / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000502:physiology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010953:Plasma Volume / Q000502:physiology*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012083:Renin / Q000097:blood; D013686:Telemetry; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; D000318:Adrenergic beta-Agonists; C119712:Agtrap protein, mouse; D007457:Iodine Radioisotopes; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000450:Aldosterone; D012083:Renin; D007545:Isoproterenol