Endothelial Vasodilator Angiotensin Receptors are Changing in Mice with Ageing

Background and aim: the vascular function of angiotensin ii-type-2 receptorsin adults is controversial. we sought their location and function in mouse aorticrings at young and old mice.methods: male c57bl mice (aged 4 and 14 months) were killed by co2. thedescending thoracic aorta was cleaned and dissected into rings. aortic rings weremounted in krebs’ solution at 37 °c and then setup in a multi-myograph. alsosegments of aorta were incubated with or without antagonists then tmrangiotensinii and/or qapb were added.results: at 4 months, angiotensin ii, at low concentrations, caused losartansensitivecontraction; higher concentrations (100nmol/l) caused relaxationsensitive to endothelial denudation, l-name or pd123319. angiotensin ii-type-1receptors blockade plus l-name revealed pd123319-sensitive contraction. atold mice, aortic relaxation to angiotensin ii was lost. at young mice, losartan andpd123319, together but not separately, abolished binding of fluorescent tmrangiotensinii, to endothelium and smooth muscle, indicatin angiotensin ii-type-1and angiotensin ii-type-2 receptors in both cell types. in contrast, at 14 monthsendothelial fluorescence was eliminated by losartan.conclusions: aortic endothelium of young adult mice has angiotensin ii-type-2receptors that release vasodilator nitric oxide. this is lost in old age, explainingage-related loss of vasodilatation by angiotensin ii. aortic smooth muscle haspro-contractile angiotensin ii-type-1 and angiotensin ii-type-2 receptors in youngand 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 atyoung ages, angiotensin ii-type-1 receptors of unknown function are present onendothelium.