Endothelial vasodilator angiotensin receptors are changing in mice with ageing

ABSTRACT

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. 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[degree sign]C and then setup in a multi-myograph. Also segments of aorta were incubated with or without antagonists then TMRAngiotensin II and/or QAPB were added. At 4 months, angiotensin II, at low concentrations, caused losartansensitive 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 TMRangiotensin 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. 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