Angiotensin II increases vascular and renal endothelin-1 and functional endothelin converting enzyme activity in vivo: role of ETA receptors for endothelin regulation

Abstract

Angiotensin II (Ang II)-stimulated expression of endothelin-1 (ET-1) mRNA is blocked by ETA antagonists in vitro. We studied effects of Ang II (200 ng/kg/min) and ETA antagonist LU135252 (50 mg/kg/d) in WKY rats in vivo investigating vascular and renal ET-1 protein expression, functional endothelin converting enzyme (ECE) activity, and clearance of (125I)ET-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 of 125IET-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-receptors in vivo.