The peptide hormone angiotensin II: its new functions in tissues and organs

The peptide hormone angiotensin II is well established to play an endocrine role in the regulation of blood pressure, fluid and electrolyte homeostasis. In addition to its hemodynamic function, recent studies have shown that numerous tissues and organs contain their own locally generated angiotensin products (angiotensin II, III, IV and Ang 1-7) and they exhibit their respective activities. Such an intrinsic angiotensin-generating system renders to specific tissue function of our body, frequently via the regulatory mechanism of a paracrine, autocrine or intracrine manner. These tissues and organs include, to name but a few, the brain, bone marrow, adipose, epididymis, carotid body, liver, and pancreas. This local system has been shown to be responsive to various stimuli of physiological and pathophysiological importance. Moreover, the locally generated angiotensin peptides have multiple and novel actions including cell growth, anti-proliferation, apoptosis, reactive oxygen species generation, hormonal secretion, pro-inflammatory, and pro-fibrogenic actions, as well as vasoconstriction and vasodilatation. Notwithstanding the emerging roles of angiotensin II in various tissues and organs, the physiological significance and ultimately the clinical relevance remain largely undefined. Future target for these new functions by making use of specific renin-angiotensin system inhibitors, such as the angiotensin-converting enzyme and angiotensin II receptor blockers either in mono-therapy or in combination, could be of clinical importance. The current review is to focus on some of the new functions arising from the locally formed angiotensin II in tissues and organs, with particular attention to its emerging roles in the liver and the pancreas.