Inhibition of angiotensin II Gq signaling augments β-adrenergic receptor mediated effects in a renal artery stenosis model of high blood pressure
| Autor: | Scott M. MacDonnell, Patrick Most, David M. Harris, Walter J. Koch, Matthieu Boucher, Susan R. Moraca, Philip Raake, Xiongwen Chen, Andrea D. Eckhart, Steven R. Houser, Stephanie Pesant, Leif Erik Vinge, Dongjun Li, Heather I. Cohn |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Cardiac function curve
Male medicine.medical_specialty Angiotensin receptor Angiotensin-Converting Enzyme Inhibitors Mice Transgenic Renal Artery Obstruction Article Muscle hypertrophy Mice Internal medicine Receptors Adrenergic beta medicine Animals Myocytes Cardiac Molecular Biology Kidney Angiotensin II receptor type 1 Angiotensin Receptor Antagonists business.industry Angiotensin II Hemodynamics medicine.anatomical_structure Endocrinology Echocardiography Hypertension Ventricular pressure GTP-Binding Protein alpha Subunits Gq-G11 Female Cardiology and Cardiovascular Medicine business Signal Transduction |
| Popis: | Chronic ventricular pressure overload states, such as hypertension, and elevated levels of neurohormones (norepinephrine, angiotensin II, endothelin-1) initiate cardiac hypertrophy and dysfunction and share the property of being able to bind to Gq-coupled 7-transmembrane receptors. The goal of the current study was to determine the role of endogenous cardiac myocyte Gq signaling and its role in cardiac hypertrophy and dysfunction during high blood pressure (BP). We induced renal artery stenosis for 8 weeks in control mice and mice expressing a peptide inhibitor of Gq signaling (GqI) using a 2 kidney, 1 clip renal artery stenosis model. 8 weeks following chronic high BP, control mice had cardiac hypertrophy and depressed function. Inhibition of cardiomyocyte Gq signaling did not reverse cardiac hypertrophy but attenuated increases in a profile of cardiac profibrotic genes and genes associated with remodeling. Inhibition of Gq signaling also attenuated the loss of cardiac function. We determined that Gq signaling downstream of angiotensin II receptor stimulation negatively impacted beta-adrenergic receptor (AR) responses and inhibition of Gq signaling was sufficient to restore betaAR-mediated responses. Therefore, in this study we found that Gq signaling negatively impacts cardiac function during high BP. Specifically, we found that inhibition of AT1-Gq signaling augmented betaAR mediated effects in a renal artery stenosis model of hypertension. These observations may underlie additional, beneficial effects of angiotensinogen converting enzyme (ACE) inhibitors and angiotensin receptor antagonists observed during times of hemodynamic stress. |
| Databáze: | OpenAIRE |
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