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AT1 Receptors, Angiotensin Receptor Blockade, and Clinical Hypertensive Disease

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Renin Angiotensin System and Cardiovascular Disease

Part of the book series: Contemporary Cardiology ((CONCARD))

Abstract

The renin angiotensin system (RAS) is a coordinated hormonal cascade, the major effector peptide of which is angiotensin II (Ang II). Ang II binds to one of two principle receptors, AT1 (AT1R) and AT2 (AT2R). AT1Rs mediate the vast majority of biological actions of the RAS, almost all of which are potentially detrimental. This chapter focuses on new developments in our knowledge of AT1Rs and the actions of angiotensin receptor blockers (ARBs) in the treatment of hypertension. Several novel mechanisms have been described whereby AT1Rs mediate detrimental actions in cardiovascular and renal function. These include [1] Ang II-independent activation of AT1Rs, which respond only to inverse agonist administration [2]; AT1R-activating autoantibodies, potentially important in the pathogenesis of pre-eclampsia and other conditions associated with inflammation [3]; G protein receptor-interacting proteins which may modulate the functional activity of AT1Rs [4]; and receptor cross-talk/receptor dimerization. New considerations of ARBs for the treatment of hypertension include [1] renal tissue RAS function independently of the systemic circulation [2], AT2R activation in response to AT1R blockade [3], pleiotropic actions of ARBs, and new data on the use of combination RAS blockade. The results of several major new clinical trials are discussed and placed in context with existing antihypertensive therapy.

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Medicine, University of VirginiaHealth System, Charlottesville, VA, USA

    Robert M. Carey MD, MACP

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  1. Robert M. Carey MD, MACP
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Correspondence to Robert M. Carey MD, MACP .

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  1. Department of Pharmacology, University of Puerto Rico, San Juan, 00936, U.S.A.

    Walmor C. DeMello

  2. Ochsner Clinic Foundation, Jefferson Highway 1514 , New Orleans, 70121, U.S.A.

    Edward D. Frohlich

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Carey, R.M. (2009). AT1 Receptors, Angiotensin Receptor Blockade, and Clinical Hypertensive Disease. In: DeMello, W., Frohlich, E. (eds) Renin Angiotensin System and Cardiovascular Disease. Contemporary Cardiology. Humana Press. https://doi.org/10.1007/978-1-60761-186-8_6

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