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.