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Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney

Department of Medicine, Duke University Medical Center and Durham Veterans Affairs Medical Center, Durham, NC 27710, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 12/2006; 103(47):17985-90. DOI: 10.1073/pnas.0605545103
Source: PubMed

ABSTRACT Essential hypertension is a common disease, yet its pathogenesis is not well understood. Altered control of sodium excretion in the kidney may be a key causative feature, but this has been difficult to test experimentally, and recent studies have challenged this hypothesis. Based on the critical role of the renin-angiotensin system (RAS) and the type I (AT1) angiotensin receptor in essential hypertension, we developed an experimental model to separate AT1 receptor pools in the kidney from those in all other tissues. Although actions of the RAS in a variety of target organs have the potential to promote high blood pressure and end-organ damage, we show here that angiotensin II causes hypertension primarily through effects on AT1 receptors in the kidney. We find that renal AT1 receptors are absolutely required for the development of angiotensin II-dependent hypertension and cardiac hypertrophy. When AT1 receptors are eliminated from the kidney, the residual repertoire of systemic, extrarenal AT1 receptors is not sufficient to induce hypertension or cardiac hypertrophy. Our findings demonstrate the critical role of the kidney in the pathogenesis of hypertension and its cardiovascular complications. Further, they suggest that the major mechanism of action of RAS inhibitors in hypertension is attenuation of angiotensin II effects in the kidney.

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    • "Focusing specifically on the impact of the renin angiotensin system, reciprocal cross-transplantations of fully vascularized kidney transplants between AT1A receptor deficient and wild type mice were performed to determine the relative importance of AT1A receptors expressed in renal (e.g., the renal epithelium, the renal vasculature or other renal components) and extra-renal (e.g., the resistance vasculature, the CNS or the adrenals) tissues for baseline blood pressure and angiotensin II induced hypertension. These studies support that the hypertensive effects of angiotensin II are predominantly dependent on renal AT1A receptors (Crowley et al., 2006). In contrast, the reduced resting blood pressure observed in AT1A deficient "
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    Frontiers in Physiology 12/2013; 4:388. DOI:10.3389/fphys.2013.00388 · 3.50 Impact Factor
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    • "The production of Ang 1-7 by BeWo cells in the absence of prorenin raises the interesting possibility that non-renin proteases exist, which can form Ang peptides within human intrauterine tissues. As far as we know this possibility has not been investigated, although a non-renin angiotensin system (chymase) has been described in the heart where Ang II plays a key role in cardiac hypertrophy [32]. "
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    Placenta 05/2012; 33(8):634-9. DOI:10.1016/j.placenta.2012.05.001 · 3.29 Impact Factor
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    • "Measurements of sodium balance were carried out as described previously (Crowley et al., 2006) with individual metabolic cages and a gel diet containing nutrients, water, and 0.1% w/w sodium (Nutra-Gel; Bio-Serv, Frenchtown, NJ). "
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