Despite intense investigation in the last decade, many questions concerning the etiology of atherosclerosis remain unanswered. Hypercholesterolemia and hypertension are clearly risk factors for the development of vascular lesions, although the precise molecular steps between elevated lipid or blood pressure levels and the development of atherosclerotic lesions are not completely defined.1,2⇓ Hypertension is frequently associated with additional risk factors such as hypercholesterolemia, estrogen deficiency, or hyperinsulinemia. This clustering of risk factors greatly enhances the probability to develop atherosclerosis.3 Nevertheless, the cellular events responsible for the mutual appearance of several risk factors are poorly understood. A series of recent studies have addressed the hypothesis that enhanced AT1 receptor activation could explain the association of various hormonal and metabolic disorders with hypertension, and ultimately, with accelerated progression of vascular lesions. As early as 1980, Alexander and colleagues discovered that the vasoconstriction caused by angiotensin II in resistance vessels was variable.4 Further investigations revealed that AT1 receptor activation is subject to a negative feedback, in that increased levels of angiotensin II diminish and decreased angiotensin II concentrations enhance AT1 receptor activation.5–8⇓⇓⇓ More recently, it has been shown that multiple agonists other than angiotensin II modulate AT1 receptor expression. This phenomenon, referred to as heterologous AT1 receptor regulation, is induced by various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), or fibroblast growth factor (FGF), all which downregulate AT1 receptor expression.9 Numerous other factors, including glucocorticoids, aldosterone, forskolin, TNFα, cytokines, nitric oxide, insulin, LDL, estrogen, progesterone, sodium, free radicals, IGF-1, and isoprenaline are known to influence AT1 receptor expression (Table). 10–38⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓ …