Endothelial Vasodilator Angiotensin Receptors are Changing in Mice with Ageing

Background: The vascular function of Angiotensin II-type-۲ receptors in adults is controversial. We sought their location and function in mouse aortic rings at young and old mice. Materials and Methods: Male C۵۷Bl mice (aged ۴ and ۱۴ months) were killed by CO۲. The descending thoracic aorta was cleaned and dissected into rings. Aortic rings were mounted in Krebs’ solution at ۳۷ °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 ۴ months, angiotensin II, at low concentrations, caused losartan-sensitive contraction higher concentrations (۱۰۰nmol/L) caused relaxation sensitive to endothelial denudation, L-NAME or PD۱۲۳۳۱۹. Angiotensin II-type-۱ receptors blockade plus L-NAME revealed PD۱۲۳۳۱۹-sensitive contraction. At old mice, aortic relaxation to angiotensin II was lost. At young mice, Losartan and PD۱۲۳۳۱۹, together but not separately, abolished binding of fluorescent TMR-angiotensin II, to endothelium and smooth muscle, indicatin Angiotensin II-type-۱ and Angiotensin II-type-۲ receptors in both cell types. In contrast, at ۱۴ months endothelial fluorescence was eliminated by losartan. Conclusion: Aortic endothelium of young adult mice has Angiotensin II-type-۲ 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-۱ and Angiotensin II-type-۲ receptors in young and old mice. Reciprocal actions of angiotensin II are, due to Angiotensin II-type-۱ and Angiotensin II-type-۲ receptors situated on different cell types but only at young ages, Angiotensin II-type-۱ receptors of unknown function are present on endothelium.