Role of angiotensin in the rostral ventrolateral medulla in the pressor response to aversive stress

Mice with global knockout of the AT 1A R have an attenuated pressor response to aversive stress. Under isoflurane anesthesia, AT 1A R knockout (AT 1A −/− ) mice were implanted with radiotelemeters to measure blood pressure (BP). After one week the mice were re‐anesthetised (75μg/g ketamine, 10μg/g xylazine IP) and replication‐deficient lentiviruses, expressing AT 1A R (n=7) or GFP (n=5) under the control of a catecholamine‐selective promoter (PRSx8) were microinjected into the RVLM bilaterally. After three weeks, mice were subjected to 5‐min restraint stress, novel food presentation, and 60‐mins in a different cage previously occupied by another male mouse (cage‐switch test). Resting BP was not affected with either virus. The BP response to the cage‐switch test was potentiated by C1 neuron expression of AT 1A R vs GFP (+22±2 mmHg vs. +10±1 mmHg). Restraint stress caused a smaller pressor response in AT 1A R vs GFP (+15±2 mmHg vs. +30±3 mmHg), whilst the response to the novel food was similar in both groups (+25±2 mmHg vs. +27±1 mmHg). The observations provide direct support for the involvement of endogenous angiotensin II acting on C1 neurons in RVLM to modulate pressor responses to aversive, but not positive stressors. Funded by the NHMRC and the Australian NHF.