Minireview: overview of the renin-angiotensin system--an endocrine and paracrine system

Since the discovery of Renin as a pressor substance in 1898, the renin-angiotensin (Ras) system has been extensively studied because it remains a prime candidate as a causative factor in the development and maintenance of hypertension. Indeed, some of the properties of the physiologically active component of the Ras, angiotensin II, include vasoconstriction, regulation of renal sodium and water absorption, and increasing thirst. Initially, its affect on blood pressure was thought to be mediated primarily through the classical endocrine pathway; that is, the generation of blood-borne angiotensin with actions in target tissues. More recently, however, it has become appreciated that a local autocrine or paracrine Ras may exist in a number of tissues, and that these may also play a significant role in regulating blood pressure. Some of the difficulties in studying tissue Ras stem from the limitations of pharmacology in not differentiating between Ras products made systemically from those synthesized locally. However, the development of transgenic Animals with highly specific promoters to target the Ras to specific tissues provided important tools to dissect these systems. Thus, this minireview will discuss recent advances in understanding the relationship between endocrine and paracrine (tissue) Ras using transgenic models.