Trends in Endocrinology & Metabolism
ReviewAngiotensin III: a central regulator of vasopressin release and blood pressure
Section snippets
Identification of the in vivo metabolic pathways of brain AngII and AngIII
Among the enzymes potentially able to hydrolyse AngII and AngIII, two membrane-bound zinc metallopeptidases 13, 14, 15, aminopeptidase A (APA: EC 3.4.11.7) and aminopeptidase N (APN: EC 3.4.11.2), are particularly good candidates for this function. It is well established that, in vitro, purified APA hydrolyses the N-terminal Asp of AngII to generate AngIII (reviewed in Ref. 16), whereas purified APN hydrolyses the N-terminal Arg of AngIII to generate AngIV (Ref. 17).
Both APA and APN have been
Brain angiotensin III and vasopressin release
Vasopressin is released from the posterior pituitary into the blood by magnocellular neurones originating from the supraoptic nucleus (SON) and paraventricular nucleus (PVN) 35. The stimulation of AVP release by AngII/III is thought to be one of the mechanisms by which AngII/III controls volume homeostasis under conditions of hypovolemia, by reducing renal water loss and increasing BP (Ref. 36).
It is now well established that AngII and AngIII, injected i.c.v. or directly into the SON or PVN,
Angiotensin III and central control of blood pressure
Several studies have tried to determine the respective roles of AngII and AngIII in the central control of BP. AngII and AngIII, injected separately i.c.v. into normotensive Wistar Kyoto (WKY) or SHR rats, cause similar dose-dependent pressor responses 24, 49, 50. This pressor response involves an increase in sympathetic nerve activity, synaptic inhibition of the baroreflex at the level of the nucleus of the tractus solitarius and the release of AVP (Ref. 11). In addition, the
Conclusion and perspectives
Brain AngIII, generated by APA, seems to be a major effector peptide of the central RAS in the control of AVP release and BP. Brain AngIII exerts a tonic stimulatory effect on BP. Therefore, the inhibition of central, but not peripheral, APA with specific and selective inhibitors leads to a decrease in BP. Thus, central APA might be an interesting candidate target for the treatment of hypertension, which justifies the development of potent and selective APA inhibitors that cross the blood–brain
Acknowledgements
We are grateful to P. Corvol and B.P. Roques for critical reading of the article. The text was edited by J. Sappa (Alex Edelman and Associates). This work was supported by the INSERM and CNRS Institutes.
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