Changes in ET(A)-, AT1- and AT2-receptors in the phenotypically transformed intimal smooth muscle layer of human atherosclerotic coronary arteries.
The aim of this study was to examine, using autoradiography, the distribution of endothelin (ET) and angiotensin receptors in the two phenotypic states of normal (NCA) and atherosclerotic human coronary arteries [coronary artery disease (CAD)]. ET and angiotensin receptors in epicardial coronary arteries were visualized with 0.1 nM [125I]ET-1 and 0.4nM [125I]Sar1, Ile8 angiotensin-II, respectively. Developed images were quantified using computer-assisted densitometry. In both NCA and CAD vessels the density of ET(A)-receptors was much greater in the medial compared to the intimal smooth muscle layer. ET(B)-receptors were predominantly localized to perivascular nerves in NCA and CAD. Overall binding of angiotensin II to the media of NCA was significantly greater than to the intimal layer. The angiotensin type I receptor (AT1) predominated in both the media and intima of NCA and this subtype was downregulated with CAD. Fewer angiotensin type 2 receptors (AT2) were found in the media of NCA with a significant upregulation of AT2 in both the media and the thickened intima of CAD.
Katugampola
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SD
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, UK. sdk23@hermes.cam.ac.uk
Davenport
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AP
D000328:Adult; D003324:Coronary Artery Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000737:chemistry*; D010641:Phenotype; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D044022:Receptor, Endothelin A; D011945:Receptors, Angiotensin / Q000032:analysis*; D017466:Receptors, Endothelin / Q000032:analysis*
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D044022:Receptor, Endothelin A; D011945:Receptors, Angiotensin; D017466:Receptors, Endothelin