AimsThe caudal ventrolateral medulla (CVLM) is important for autonomic regulation and is rich in angiotensin II type 1A receptors (AT1AR). To determine their function, we examined whether the expression of AT 1AR in the CVLM of mice lacking AT1AR (AT 1A -/-) alters baroreflex sensitivity and cardiovascular responses to stress.Methods and resultsBilateral microinjections into the CVLM of AT1A -/- mice of lentivirus with the phox-2 selective promoter (PRSx8) were made to express either AT1AR (Lv-PRSx8-AT 1A) or green fluorescent protein (Lv-PRSx8-GFP) as a control. Radiotelemetry was used to record mean arterial pressure (MAP), heart rate (HR), and locomotor activity. Following injection of Lv-PRSx8-GFP, robust neuronal expression of GFP was observed with ∼60 of the GFP-positive cells also expressing the catecholamine-synthetic enzyme tyrosine hydroxylase. After 5 weeks, there were no differences in MAP or HR between groups, but the Lv-PRSx8-AT1A-injected mice showed reduced baroreflex sensitivity (-25, P 0.003) and attenuated pressor responses to cage-switch and restraint stress compared with the Lv-PRSx8-GFP-injected mice. Reduced MAP mid-frequency power during cage-switch stress reflected attenuated sympathetic activation (Pgroup × stress 0.04). Fos-immunohistochemistry indicated greater activation of forebrain and hypothalamic neurons in the Lv-PRSx8-AT1A mice compared with the control.ConclusionThe expression of AT1AR in CVLM neurons, including A1 neurons, while having little influence on the basal blood pressure or HR, may play a tonic role in inhibiting cardiac vagal baroreflex sensitivity. However, they strongly facilitate the forebrain response to aversive stress, yet reduce the pressor response presumably through greater sympatho-inhibition. These findings outline novel and specific roles for angiotensin II in the CVLM in autonomic regulation.
- Angiotensin type 1A receptor
- Baroreflex gain
- Cardiovascular stress response
- Caudal ventrolateral medulla