Endothelial Vasodilator Angiotensin Receptors are Changing in Mice with Ageing

Background: The vascular function of Angiotensin II-type-2 receptors in adults is controversial. We sought their location and function in mouse aortic rings at young and old mice. Materials and Methods: Male C57Bl mice (aged 4 and 14 months) were killed by CO2. The descending thoracic aorta was cleaned and dissected into rings. Aortic rings were mounted in Krebs’ solution at 37 °C and then setup in a multi-myograph. Also segments of aorta were incubated with or without antagonists then TMR-Angiotensin II and/or QAPB were added.  Results: At 4 months, angiotensin II, at low concentrations, caused losartan-sensitive contraction higher concentrations (100nmol/L) caused relaxation sensitive to endothelial denudation, L-NAME or PD123319. Angiotensin II-type-1 receptors blockade plus L-NAME revealed PD123319-sensitive contraction. At old mice, aortic relaxation to angiotensin II was lost. At young mice, Losartan and PD123319, together but not separately, abolished binding of fluorescent TMR-angiotensin II, to endothelium and smooth muscle, indicatin Angiotensin II-type-1 and Angiotensin II-type-2 receptors in both cell types. In contrast, at 14 months endothelial fluorescence was eliminated by losartan. Conclusion: Aortic endothelium of young adult mice has Angiotensin II-type-2 receptors that release vasodilator nitric oxide. This is lost in old age, explaining age-related loss of vasodilatation by Angiotensin II. Aortic smooth muscle has pro-contractile Angiotensin II-type-1 and Angiotensin II-type-2 receptors in young and old mice. Reciprocal actions of angiotensin II are, due to Angiotensin II-type-1 and Angiotensin II-type-2 receptors situated on different cell types but only at young ages, Angiotensin II-type-1 receptors of unknown function are present on endothelium.