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(Circulation. 1999;100:2131.)
© 1999 American Heart Association, Inc.
Brief Rapid Communications |
Statin-Sensitive Dysregulated AT1 Receptor Function and Density in Hypercholesterolemic Men
From the Klinik III für Innere Medizin and Klinik II für Innere Medizin (F.J.),Universität Köln, Germany.
Correspondence to Dr Georg Nickenig, Klinik III für Innere Medizin, Universität zu Köln, Joseph-Stelzmann-Str 9 50924 Köln. E-mail georg.nickenig{at}uni-koeln.de
Background—Hypercholesterolemia causes an upregulation of vascular angiotensin II type 1 (AT1) receptor expression in cell culture and animal models. The presented studies were undertaken to examine AT1 receptor overexpression in hypercholesterolemic men and therapeutic interventions thereof by HMG CoA reductase inhibitors (statins).
Methods and Results—Effects of AT1 receptor activation were measured by assessing the blood pressure increase after infusion of angiotensin II in normo- (cholesterol 181±11 mg/dL) and hypercholesterolemic (cholesterol 294±10 mg/dL) men (n=19 and 20, respectively). AT1 receptor expression was assessed on isolated platelets. Some patients were investigated before and after cholesterol-lowering therapy with statins. Hypercholesterolemia led to a significant increase of angiotensin II-induced blood pressure elevation. AT1 receptor expression was significantly enhanced in hypercholesterolemic individuals (Bmax=5.2±1.2 fmol/mg protein) compared with normocholesterolemic men (Bmax=2.1±0.2 fmol/mg protein). Cholesterol-lowering treatment with statins reversed the elevated blood pressure response to angiotensin II infusion (P<0.05) and downregulated AT1 receptor density (P<0.05).
Conclusions—Hypercholesterolemia induces AT1 receptor overexpression and enhances biological effects of angiotensin II in men. These findings provide novel insights into the pathogenesis of hypertension and atherosclerosis and may initiate rational and new therapeutic concepts.
Key Words: lipids • hypertension • angiotensin • receptors • atherosclerosis
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