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The renin–angiotensin–aldosterone (RAA) system and the endothelin (ET) system entail the most potent vasopressor mechanisms identified to date. Although they were studied in depth in relation to arterial hypertension and cardiovascular diseases, limited information on their interrelationships in causing hypertension and related target organ damage exists. The identification of consensus sequences for jun in the regulatory region of the preproendothelin-1 (ppET-1) gene raised the possibility of its transcriptional regulation by angiotensin II (Ang II). This was confirmed by the finding that stimulation with Ang II of cultured vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) induced expression of the ppET-1 gene and synthesis of ET-1. Endogenously produced ET-1 was found to contribute to the hypertrophic response of cardiomyocytes to Ang II and thereby to cardiac hypertrophy. Furthermore …