ANGIOTENSIN-II SIGNAL-TRANSDUCTION PATHWAYS IN THE CARDIOVASCULAR-SYSTEM

The renin-angiotensin system in mammals represents a complex cascade of tightly regulated proteolytic enzymes and peptide products. One important product angiotensin II (Ang-II), is a circulating hormone that displays a wide range of physiologic effects in many tissues, including those of the cardiovascular system. If is well known that Ang-II increases the contractile state of vascular smooth muscle and cardiac myocytes by triggering multiple intracellular responses following its binding to specific receptor sites. Some of the signal transduction mechanisms that underlie these responses are understood, while others are not defined at present. Further there has been much recent interest in Ang-II-evoked signaling since the renin-angiotensin system has been associated with the development of cardiovascular disease. Thus, the identification of Ang-II-stimulated signal transduction mechanisms will illuminate the underlying principles of normal hormone-regulated cardiovascular homeostasis as well as those involved in pathologic processes such as human hypertension, cardiac arrhythmias, and the cellular remodeling that follows vascular injury or sustained pressure overload. This review examines the current status and direction of our knowledge regarding Ang-II-stimulated signal transduction mechanisms in vascular smooth muscle and cardiac myocytes.