Left ventricular function in mice lacking the AT2 receptor

Objectives The role of the AT(2) receptor in the heart is incompletely understood. We investigated left ventricular performance in AT(2) receptor knockout mice, with and without deoxycorticosterone acetate (DOCA)-salt treatment. Given the putative opposing functions of the AT(1) and AT(2) receptor, we also analysed AT(1) receptor expression in the left ventricle, Methods 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 AT(1)-receptor expression by RNase-protection assays. Results In AT(2) 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. AT(2) receptor knockout mice and wildtype mice both stabilized their reduced stroke volume after laparatomy as peripheral resistance was increased. DOCA-salt treatment increased elastance in AT(2) receptor knockout mice, compared to controls. Furthermore, AT(2) receptor knockout mice had a steeper increase in dP/dt(max). Left ventricular AT(1) receptor gene expression was increased in AT(2) receptor knockout mice and was not down-regulated in response to DOCA-salt treatment. Finally, the hearts of AT(2) receptor knockout mice were smaller than controls, but increased in size in response to DOCA-salt treatment. Conclusions AT(2) 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 AT(2) receptor may be important to AT(1) receptor expression in response to DOCA-salt challenge and may have some influence on cardiac growth responses, J Hypertens 19:967-976 (C) 2001 Lippincott Williams & Wilkins.