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. beta-Adrenergic receptors were also measured by binding of 125I-iodocyanopindolol with the beta 1 and beta 2 fractions determined by use of a beta 1-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 AT1 density was greater in the IDC than in the ISC left ventricles (IDC: 2.73 +/- 0.40, P < .01; ISC: 3.89 +/- 0.39 fmol/mg protein, P = NS versus nonfailing). beta 1 but not beta 2 density was decreased in the failing left ventricles. AT1 density was correlated with beta 1 density in all left ventricles (r = .43). AT1 density was also decreased in IDC right ventricles. In situ reverse transcription-polymerase chain reaction in sections of nonfailing and failing ventricles indicated that AT1 mRNA was present in both myocytes and nonmyocytes. CONCLUSIONS: AT1 receptors are selectively downregulated in failing human ventricles, similar to the selective downregulation of beta 1 receptors. The relative lack of AT1 downregulation in ISC hearts may be related to differences in the degree of ventricular dysfunction.
Subject(s)
Cardiomyopathy, Dilated/metabolism , Heart Failure/metabolism , Myocardium/metabolism , Receptors, Angiotensin/biosynthesis , Adult , Angiotensin II/analogs & derivatives , Angiotensin II/metabolism , Cell Membrane/metabolism , Down-Regulation , Female , Heart Failure/pathology , Heart Ventricles , Humans , Kinetics , Male , Myocardium/pathology , Polymerase Chain Reaction , Radioligand Assay , Receptor, Angiotensin, Type 1 , Receptor, Angiotensin, Type 2 , Receptors, Adrenergic, beta-1/metabolism , Receptors, Adrenergic, beta-2/metabolism , Reference ValuesABSTRACT
Hybridization sites of an rDNA probe coding for the 5.8S, 18S and 26S genes were detected on the chromosomes of sugarcane and a related genus, Erianthus, using fluorescence in situ hybridization. One unpaired and five paired hybridization sites were detected in a Saccharum spp. hybrid. A first introgression hybrid (I1) between Saccharum officinarum and Saccharum spontaneum had seven pairs of hybridization sites. A clone of Erianthus arundinaceus showed six hybridization sites in somatic tissue.
