Angiotensin II type 2 receptors mediate nNOS‐dependent nitric oxide production in neurons of the dorsomedial nucleus tractus solitarius (dmNTS).

Angiotensin II (AngII) has powerful effects on dmNTS, a region involved in the central mechanisms of hypertension. However, the relative contribution of AngII AT 1 and AT 2 receptors (R) in dmNTS neurons remains unclear. Activation of AT 1 R leads to production of reactive oxygen species (ROS), which, in turn, alter Ca 2+ homeostasis in dmNTS neurons (Hypertension, 2006, 48:482). Activation of AT 2 R may increase nitric oxide (NO) production, and NO can act as a ROS scavenger. Therefore, we used isolated dmNTS neurons to examine if activation of AT 2 R, via NO, reduces ROS availability. dmNTS neurons were immunoreactive for AT 2 R and neuronal NO synthase (nNOS). Following AT 1 R inhibition with losartan, AngII (30nM‐4μM) attenuated ROS production (6.2±2.1%;n=6, p<0.05), assessed by the dye C‐DCDHF‐DA, and the reduction was abolished by the AT 2 R antagonist PD123319. The ROS increase induced by AngII (33±5%;n=16, p<0.05) was enhanced (p<0.05) by the NOS inhibitor L‐NNA (83±20%;n=7), PD123319 (67±20%;n=5) and in dmNTS neurons of nNOS−/− mice (60±13%;n=9). The AT 2 R agonist CGP42112A increased NO production (9±3%;n=8;p<0.05), assessed by DAF‐FM. The data suggest that activation of AT 2 R stimulates production of NO which, in turn, reduces ROS availability in the dmNTS neurons. AT 2 R‐derived NO could mitigate the effects of AT 1 R‐derived ROS and counterbalance the deleterious actions of AngII in dmNTS (Supported by HL‐18974).