Angiotensin type 1A receptor expression in C1 neurons of the rostral ventrolateral medulla contributes to the development of angiotensin‐dependent hypertension

New Findings What is the central question of this study? This study addresses the mechanism by which deletion of angiotensin II type 1A receptors from catecholaminergic neurons reduces angiotensin‐dependent hypertension, as well as the identity of the cells involved. What is the main finding and its importance? Deletion of angiotensin II type 1A receptors from catecholaminergic neurons results in reduced sympathetic nerve activation and fluid and electrolyte retention during angiotensin infusion. The C1 neurons of the rostral ventrolateral medulla are involved in the later phase of the hypertension. We demonstrate that at least two different populations of catecholaminergic neurons are involved in the sympathetic nerve activation required for the full development of angiotensin‐dependent hypertension. Chronic low‐dose systemic infusion of angiotensin II induces hypertension via activation of the angiotensin II type 1A receptor (AT 1A R). Previously, we have demonstrated that expression of the AT 1A R on catecholaminergic neurons is necessary for the full development of angiotensin‐dependent hypertension. In the present study, we examined the mechanism by which selective deletion of the AT 1A R from these cells affects the development of hypertension. We also tested the hypothesis that AT 1A Rs expressed by catecholaminergic C1 neurons in the rostral ventrolateral medulla play an important role in angiotensin‐induced hypertension. A Cre‐lox approach was used to delete the AT 1A R from all catecholaminergic cells or from C1 neurons selectively. Subcutaneous administration of angiotensin II induced hypertension in all mice, with delayed onset and reduced maximal response in the global AT 1A R catecholaminergic knockout mice. The AT 1A R catecholaminergic knockout mice had decreased renal fluid and electrolyte retention and urinary noradrenaline excretion. The blood pressure response was reduced only during the second week of angiotensin II infusion in the mice with selective C1 AT 1A R deletion, demonstrating that AT 1A R expression by C1 neurons plays a moderate role in angiotensin‐induced hypertension. The difference in the time course of development of hypertension between the mice with global AT 1A R knockout from catecholaminergic cells and the mice with C1 AT 1A R deletion suggests that other catecholaminergic neurons are important.