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

The renin-angiotensin system in mammals represents a complex cascade o f tightly regulated proteolytic enzymes and peptide products. One impo rtant product angiotensin II (Ang-II), is a circulating hormone that d isplays a wide range of physiologic effects in many tissues, including those of the cardiovascular system. If is well known that Ang-II incr eases the contractile state of vascular smooth muscle and cardiac myoc ytes by triggering multiple intracellular responses following its bind ing to specific receptor sites. Some of the signal transduction mechan isms that underlie these responses are understood, while others are no t defined at present. Further there has been much recent interest in A ng-II-evoked signaling since the renin-angiotensin system has been ass ociated with the development of cardiovascular disease. Thus, the iden tification of Ang-II-stimulated signal transduction mechanisms will il luminate the underlying principles of normal hormone-regulated cardiov ascular homeostasis as well as those involved in pathologic processes such as human hypertension, cardiac arrhythmias, and the cellular remo deling that follows vascular injury or sustained pressure overload. Th is review examines the current status and direction of our knowledge r egarding Ang-II-stimulated signal transduction mechanisms in vascular smooth muscle and cardiac myocytes.