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Angiotensin II Increases Vascular and Renal Endothelin-1 and Functional Endothelin Converting Enzyme Activityin Vivo:Role of ETAReceptors for Endothelin Regulation

1997; Elsevier BV; Volume: 238; Issue: 3 Linguagem: Inglês

10.1006/bbrc.1997.7394

1090-2104

Matthias Barton, Sidney Shaw, Livius V. d’Uscio, Pierre Moreau, Thomas F. Lüscher,

Receptor Mechanisms and Signaling

Angiotensin II (Ang II)-stimulated expression of endothelin-1 (ET-1) mRNA is blocked by ETAantagonistsin vitro.We studied effects of Ang II (200 ng/kg/min) and ETAantagonist LU135252 (50 mg/kg/d) in WKY ratsin vivoinvestigating vascular and renal ET-1 protein expression, functional endothelin converting enzyme (ECE) activity, and clearance of125IET-1. Infusion of Ang II for two weeks increased ET-1 protein content in aorta (4.7-fold) and femoral artery (1.6-fold) with and without endothelium and in kidneys (3-fold, p<0.05) and enhanced functional ECE activity (p<0.05). The Ang II-induced increase in tissue ET-1 content and functional ECE activity was completely prevented by LU135252 (p<0.05). Chronic treatment of control animals with LU135252 lowered basal vascular but not renal ET-1 content (p<0.05 vs. control). Clearance of125IET-1 was unaffected by the treatments. It is concluded that Ang II increases ET-1 protein and functional ECE activity in vascular smooth muscle and kidney through ETA-receptorsin vivo.