Genetically altered animal models for Mas and Angiotensin-(1-7)

Mas is the receptor for angiotensin-(1-7) and involved in cardiovascular and neuronal regulation, in which also the heptapeptide plays a major role. Mas-deficient mice were previously generated by us and their characterization showed that Mas has important functions in behaviour and cardiovascular regulation. These mice exhibit increased anxiety but despite an enhanced long-term potentiation in the hippocampus are not performing better in learning paradigms. When Mas-deficient mice are backcrossed to the FVB/N genetic background a cardiovascular phenotype is uncovered: the backcrossed animals become hypertensive. Concordant with our detection by fluorescent in-situ hybridization of Mas-mRNA in mouse endothelium, this phenotype is caused by endothelial dysfunction based on a dysbalance between nitric oxide and reactive oxygen species in the vessel wall. In agreement with these data, transgenic SHR-SP-rats overexpressing ACE2 in the vessel wall exhibit reduced blood pressure due to an improved endothelial function. Moreover, angiotensin-(1-7) overexpression in transgenic rats has cardioprotective and hemodynamic affects. In conclusion, the angiotensin-(1-7) / Mas axis has important functional implications in vascular regulation and blood pressure control in particular in pathophysiological situations