Selective Downregulation of the Angiotensin II AT 1 -Receptor Subtype in Failing Human Ventricular Myocardium

Abstract
Background The regulation of angiotensin II receptors and the two major subtypes (AT1 and AT2) in chronically failing human ventricular myocardium has not been previously examined. Methods and Results Angiotensin II receptors were measured by saturation binding of 125I-[Sar1,Ile8]angiotensin II in crude membranes from nonfailing (n=19) and failing human left ventricles with idiopathic dilated cardiomyopathy (IDC; n=31) or ischemic cardiomyopathy (ISC; n=21) and membranes from a limited number of right ventricles in each category. The AT1 and AT2 fractions were determined by use of an AT1-selective antagonist, losartan. β-Adrenergic receptors were also measured by binding of 125I-iodocyanopindolol with the β1 and β2 fractions determined by use of a β1-selective antagonist, CGP20712A. AT1 but not AT2 density was significantly decreased in the combined (IDC+ISC) failing left ventricles (nonfailing: AT1 4.66±0.48, AT2 2.73±0.39; failing: AT1 3.20±0.29, AT2 2.70±0.33 fmol/mg protein; mean±SE). The decrease in ...

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