title: Endothelin A receptor blockade prevents capillary/myocyte mismatch in the heart of uremic animals.
abstract: In the heart of uremic animals and patients, the number of capillaries per volume of myocardium is reduced. Immunohistochemical studies demonstrated increased cardiac endothelin-1 (ET-1) expression in the left ventricle of uremic animals. Therefore, whether treatment with a selective ET(A)-receptor antagonist prevented such capillary-myocyte mismatch was investigated. Twenty-four h after subtotal nephrectomy, rats were left untreated or started on treatment with the ET(A)-receptor antagonist LU 135252 (20 mg/kg per d) and with the angiotensin-converting enzyme (ACE) inhibitor trandolapril (0.3 mg/kg per d), respectively. BP was monitored by telemetry. Myocardial capillary length density was analyzed by stereologic techniques that avoid anisotropy artifacts. In addition, cardiac ET-1 protein and mRNA were measured using immunohistochemistry, in situ hybridization, and quantitative reverse transcription-PCR. Changes in cardiac ET(A)-and ET(B)-PCR. receptor mRNA were measured using reverse transcription-PCR. Fifteen wk after subtotal nephrectomy, significantly reduced left ventricular capillary length density (3307 +/- 535 mm/mm(3)) was found compared with sham-operated controls (3995 +/- 471 mm/mm(3)); this was also seen in animals that were treated with trandolapril (3503 +/- 533 mm/mm(3)) but not in animals that were treated with LU 135252 (3800 +/- 303 mm/mm(3)). The results support a role of ET-1 in the genesis of left ventricular capillary/myocyte mismatch in uremia.
authors.affiliation: Departments of Pathology, University of Heidelberg, Heidelberg, Germany.|Departments of Pathology, University of Erlangen, Erlangen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.affiliation: Department of Internal Medicine, Knoll AG, Ludwigshafen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Münter
authors.affiliation: Departments of Pathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Wessels
authors.affiliation: Department of Internal Medicine, Heidelberg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wagner
authors.affiliation: Departments of Pathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Vitali
authors.initials: V
authors.lastname: Balajew
authors.affiliation: Department of Internal Medicine, Knoll AG, Ludwigshafen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hergenröder
authors.affiliation: Departments of Pathology, University of Darmstadt, Darmstadt, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Mall
authors.affiliation: Department of Internal Medicine, Heidelberg, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002196:Capillaries / Q000473:pathology; D003326:Coronary Circulation / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008967:Molecular Biology / Q000379:methods; D009206:Myocardium / Q000473:pathology*; D009392:Nephrectomy / Q000379:methods; D010666:Phenylpropionates / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D014511:Uremia / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D007211:Indoles; D010666:Phenylpropionates; D011743:Pyrimidines; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; C052035:trandolapril; C107831:darusentan