The study of the molecular mechanisms by which angiotensin II effects the regulation of body fluid volumes and blood pressure has experienced a remarkable impetus in recent years thanks to the efforts of both physiologists and clinicians. Cloning of angiotensin II receptor subtypes and the synthesis of orally active and selective angiotensin II antagonists to AT1 and AT2 receptors has accelerated the uncovering of additional regulatory actions, which only indirectly impinge upon the blood pressure control mechanisms. From the early concept of a circulating renin–angiotensin system (RAS), knowledge has evolved to identification of the chemical machinery for the formation of angiotensin peptides in the interstitial microenvironment of diverse tissues, and the suggestion that angiotensin II synthesis may occur within the cell itself. Clinically, type 1 angiotensin II antagonists have proven beneficial in retarding or even reversing the cardiovascular sequela of hypertensive disease [1–3], and even demonstrated that blockade of angiotensin II actions may interfere with the mechanisms by which atherosclerosis progresses or develops [4, 5].

Overwhelmingly, the study of the regulatory actions of the RAS in the preservation of homeostatic processes remains focused on angiotensin II and its effects on blood pressure, cardiac and vascular mechanisms. Hypertension research has ignored the fact that the component of the RAS exists in annelids, crustaceans, molluscs, leeches and insects, invertebrates whose survival as biological entities has little to do with blood pressure regulation or cardiovascular remodelling [6]. Interestingly, in these biological entities angiotensin II, angiotensin-(2-8) and angiotensin-(3-8) participate in osmoregulation, immune mechanisms and neurotransmission, findings that should raise questions as to the primordial functions of angiotensin peptides. In this issue of the journal, Cesari et al.[7] review the current biochemical and physiological evidence for the actions