Left ventricular function in mice lacking the AT2 receptor.

Abstract

The role of the AT2 receptor in the heart is incompletely understood. We investigated left ventricular performance in AT2 receptor knockout mice, with and without deoxycorticosterone acetate (DOCA)-salt treatment. Given the putative opposing functions of the AT1 and AT2 receptor, we also analysed AT1 receptor expression in the left ventricle. We used a miniaturized conductance-manometer system to measure pressure-volume loops for analysing left ventricular performance under baseline conditions and after increasing peripheral vascular resistance. We determined left ventricular AT1-receptor expression by RNase-protection assays. In AT2 receptor knockout mice, end-systolic and end-diastolic volumes were lower than in wild-type mice, so that pressure-volume loops were shifted leftward. Left ventricular systolic and diastolic kinetics were not different between the groups. AT2 receptor knockout mice and wild-type mice both stabilized their reduced stroke volume after laparatomy as peripheral resistance was increased. DOCA-salt treatment increased elastance in AT2 receptor knockout mice, compared to controls. Furthermore, AT2 receptor knockout mice had a steeper increase in dP/dtmax. Left ventricular AT1 receptor gene expression was increased in AT2 receptor knockout mice and was not down-regulated in response to DOCA-salt treatment. Finally, the hearts of AT2 receptor knockout mice were smaller than controls, but increased in size in response to DOCA-salt treatment. AT2 receptor knockout mice displayed no major changes in left ventricular function at baseline or in response to DOCA-salt treatment, compared to wild-type mice. The AT2 receptor may be important to AT1 receptor expression in response to DOCA-salt challenge and may have some influence on cardiac growth responses.