Angiotensin-[1-7]: evidence for novel actions in the brain

Structure-activity studies of angiotensin II (Ang II) have clearly established that the carboxyl-terminal phenylalanine is crucial for activation of angiotensin receptors associated with a broad range of effects including vasoconstriction, aldosterone release, and dipsogenesis. Thus, the heptapeptide angiotensin-[1-7] (Ang-[1-7]) has been classified as an inactive metabolite of the hormone Ang II. This assumption was seriously questioned in light of the report from our laboratory that Ang-[1-7] is the major metabolite of dog brainstem homogenates both in the absence and in the presence of angiotensin-converting enzyme inhibitors. These data raised the possibility of a functional role for Ang-[1-7] in the brain. Subsequent studies in the in vitro hypothalamoneurohypophysial system of the rat demonstrated that Ang-[1-7] is equipotent with Ang II in its activation of AVP release. Other Ang II-like actions have since been identified for Ang-[1-7] in the brain. For example, microinjection of Ang-[1-7] into brainstem nuclei of the rat promotes bradycardia and hypotension; in addition, Ang-[1-7] mimics the effect of Ang II in augmenting the intrinsic discharge rate of neurons within the vagal-solitary complex of the dog. Our laboratory has also provided evidence for synthesis and storage of Ang-[1-7] in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)