Elevated central concentrations of the vasopressor octapeptide angiotensin (Ang) II increase the water intake in mammals. Recently, we showed that central AngII is also crucial in alcohol-consuming behavior. Since the heptapeptide AngIII, an AngII metabolite, is discussed to mediate AngII-related effects, we investigated water and alcohol consumption in mice, genetically deficient in aminopeptidase A (APA), a peptidase responsible for AngII conversion to AngIII. Sixteen male APA-deficient mice and their age matched wild-type controls were monitored on their water intake under basal conditions and total fluid and alcohol intake before and after social stress in a two-bottle free-choice paradigm. Alterations were connected to the regulation in activity of Ang-related peptidases (APA, ACE; ACE2) in brain regions involved in alcohol intake and peripheral organs. In comparison to their wild-type controls, APA-deficient mice drank significantly more water but not more alcohol at all investigated time points. A reduction in water intake, as observed in wild-type animals after social stress, did not occur in knockout mice. However, the reduction in alcohol consumption after social stress was significantly reduced in both strains. Alcohol consumption upregulated all three peptidases in the kidney, but not in lung. Notable, renal ACE2 activity was significantly higher in APA-deficient mice under basal condition. While the inhibition of AngII metabolism to AngIII does not influence the alcohol intake, water consumption in mice deficient for APA was significantly elevated. These differences induced by an altered AngII/AngIII ratio oppose the hypothesis that central AngII and AngIII act in a congruent pattern.

Alcohol, Aminopeptidase A, Knockout mice, Renin-angiotensin system
dx.doi.org/10.1016/j.regpep.2006.06.001, hdl.handle.net/1765/66255
Regulatory Peptides
Department of Pharmacology

Faber, F, Gembardt, F, Sun, X, Mizutani, S, Siems, W.-E, & Walther, T. (2006). Lack of angiotensin II conversion to angiotensin III increases water but not alcohol consumption in aminopeptidase A-deficient mice. Regulatory Peptides, 136(1-3), 130–137. doi:10.1016/j.regpep.2006.06.001