The cellular biology of angiotensin: paracrine, autocrine and intracrine actions in cardiovascular tissues.

A growing body of evidence suggests that angiotensin II, the effector protein of the renin-angiotensin system, is intimately involved with cell growth in target tissues. Most recently, evidence has been provided to indicate that angiotensin II is capable of inducing a hypertrophic response in cultured arterial smooth muscle cells. At the same time, considerable evidence has been developed to indicate that local analogs of the systemic renin-angiotensin system exist in multiple tissues and, in particular, in the vascular wall and the heart. Finally, data have accumulated to indicate that local growth regulatory factors, in many instances operating through regulation of proto-oncogene transcription, are involved in the hypertrophic and hyperplastic sequelae of hypertension. Included amongst these growth factors is angiotensin II. Thus, accumulating data indicate that angiotensin II is a growth factor with potential implications for the development of the sequelae of hypertension. In addition, studies from this laboratory and others suggest that angiotensin acts at least partially through what we have called an "intracrine" mechanism to produce its effects. In these multiple actions, angiotensin may provide a paradigm for other peptide growth factors and hormones.