Genetically altered animal models for Mas and angiotensin-(1-7).
Mas is the receptor for angiotensin-(1-7) and is involved in cardiovascular and neuronal regulation, in which the heptapeptide also plays a major role. Mas-deficient mice have been generated by us, and their characterization has shown 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, do not perform better in learning experiments. When Mas-deficient mice are backcrossed to the FVB/N genetic background, a cardiovascular phenotype is uncovered, in that 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 spontaneously hypertensive stroke-prone rats overexpressing ACE2 in the vessel wall exhibit reduced blood pressure as a result of improved endothelial function. Moreover, angiotensin-(1-7) overexpression in transgenic rats has cardioprotective and haemodynamic effects. In conclusion, the angiotensin-(1-7)-Mas axis has important functional implications for vascular regulation and blood pressure control, particularly in pathophysiological situations.
D000803:Angiotensin I / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics* / Q000502:physiology*; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000803:Angiotensin I; C118790:angiotensin I (1-7)