Cardiovascular characterization of mice deficient in all three angiotensin II receptors

Angiotensin (Ang) II activates AngII type 1 (AT1) and AngII type 2 (AT2) receptors. In rodents two subtypes of AT1 have been identified (AT1A and AT1B). The vasoconstrictor and growth‐stimulatory effects of Ang II are mediated by AT1. AT2 receptors are assumed to counteract these actions. To determine receptor‐specific functions and possible AngII effects independent of its known receptors, we generated mice lacking one, two, or all three AngII receptor subtypes. All combinations were vital and fertile, although survival in AT1A/AT1B‐double‐ and in the triple‐knockout mice was significantly impaired. We characterized renal and cardiac histological alterations and linked them to the absence of the generated receptor combinations. Basal blood pressure was measured in anesthetized mice by carotis canulation. We determined the reactivity to AngII infusion in those mice in vivo and in a Langendorff setting. The general vascular behaviour was characterized using vasorelaxants and AngII‐independent vasoconstrictors. We finally correlated identified differences in cardiovascular regulation to altered receptor expression and/or changes in endogenous AngII concentrations. Using a wide range of experimental settings we could identify specific functions for each of the three receptors in cardiovascular regulation and determined AngII effects independent of its receptors in triple knockout mice.