Cardiovascular phenotype of mice lacking all three subtypes of angiotensin II receptors

Angiotensin II activates two distinct receptors, the angiotensin II receptors type 1 (AT1) and type 2 (AT2). In rodents, two AT1 subtypes were identified (AT1a and AT1b). To determine receptor-specific functions and possible angiotensin II effects independent of its three known receptors we generated mice deficient in either one of the angiotensin II receptors, in two, or in all three (triple knockouts). Triple knockouts were vital and fertile, but survival was impaired. Hypotension and renal histological abnormalities in triple knockouts were comparable to those in mice lacking both AT1 subtypes. All combinations lacking AT1a were distinguished by reduced heart rate. AT1a deletion impaired the in vivo pressor response to angiotensin II bolus injection, whereas deficiency for AT1b and/or AT2 had no effect. However, the additional lack of AT1b in AT1a-deficient mice further impaired the vasoconstrictive capacity of angiotensin II. Although general vasoconstrictor properties were not changed, angiotensin II...