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Insights into angiotensin II receptor function through AT2 receptor knockout mice

Item Type:Article
Title:Insights into angiotensin II receptor function through AT2 receptor knockout mice
Creators Name:Gross, V. and Obst, M. and Luft, F.C.
Abstract:Angiotensin II signals via at least two receptors termed AT1 and AT2. The function of the AT1 receptor is well defined, while that of the AT2 receptor is still shrouded in uncertainty. AT2 gene-deficient (−/−) mice have been helpful in unravelling the function of the AT2 receptor. We have studied AT2−/− and AT2+/+ mice with classical physiological techniques developed for the rat. We found that although AT2−/− mice have normal glomerular filtration rate, the pressure–natriuresis relationship in these mice, compared with AT2+/+ mice, is shifted rightward. Moreover, medullary blood flow fails to increase with increased perfusion pressure while the AT1 receptor expression in the kidneys is increased. We used telemetry and found that AT2−/− mice have about 10 mmHg higher blood pressures than AT2+/+ mice and that their circadian rhythm is disturbed. Moreover, their baroreflexes, as measured by spectral analyses, differs from AT2+/+ controls. The cardiac function of AT2−/− mice is remarkably preserved and the differences are subtle. However, if the mice are given l-NAME hypertension, they exhibit an end-systolic pressure–volume relationship that reveals decreased contractility and probable increased vascular stiffness. Furthermore, the hearts of AT2−/− mice hypertrophy more in response to l-NAME than those of AT2+/+ mice and perivascular fibrosis is increased. DOCA-salt treatment also shows a more rightward pressure–natriuresis relationship in AT2−/− compared with AT2+/+ mice. The renal iNOS expression is increased with DOCA-salt treatment. Our findings support the notion that the AT2 receptor signals antiproliferative and antifibrotic effects and that its presence results in lower blood pressures and lesser responses to secondary forms of hypertension. Technical advances that have allowed us to adapt methods for the rat to the much smaller mouse have facilitated our studies.
Keywords:AT2 Receptor Knockout Mouse, Baroreflex, Left Ventricular Performance, Renal Function, Animals, Mice
Source:Acta Physiologica ScandinavicaActa Physiologica ScandinavicaActa Physiologica Scandinavica
Publisher:Blackwell Publishing
Page Range:487-494
Date:1 August 2004
Official Publication:https://doi.org/10.1111/j.1365-201X.2004.01322.x
PubMed:View item in PubMed

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