Different isoforms of nitric oxide synthase are involved in angiotensin-(1-7)-mediated plasticity changes in the amygdala in a gender-dependent manner.

BACKGROUND

The amygdala receives afferent sensory input and processes information related to hydromineral balance. Angiotensin acts on and through the amygdala to stimulate thirst and sodium appetite. In addition, different angiotensins seem to play a role in cognition and learning mechanisms by acting on and through the amygdala. Recently, we showed that angiotensin-(1-7) (Ang-(1-7)) enhances the magnitude of long-term potentiation (LTP) in the lateral nucleus of the amygdala (LA) via the Mas receptor.

METHODS

Extracellular field potentials were measured in the LA.

RESULTS

LA-LTP induced by stimulation of the external capsule was nitric oxide (NO)-dependent because the NO synthase (NOS) inhibitor L-NAME reduced LA-LTP. The LA-LTP was also reduced in both male and female nNOS and eNOS knockout mice. In male eNOS(-/-) mice, Ang-(1-7) enhanced LA-LTP, whereas the LTP-enhancing effect of Ang-(1-7) was missing in female eNOS(-/-) mice. Therefore, the LTP-enhancing effect of Ang-(1-7) was mediated by eNOS in females. In contrast, Ang-(1-7) strongly enhanced the LTP in nNOS(-/-) females, whereas the effect of Ang-(1-7) was missing in nNOS(-/-) males. Thus, Ang-(1-7) induced an increase in the magnitude of LTP via the involvement of nNOS in males.

CONCLUSION

Our data support not only the hypothesis that NO contributes to plasticity changes in the lateral amygdala, but also show for the first time a gender-dependent involvement of different isoforms of NOS in the mediation of Ang-(1-7) on LTP in the amygdala.