Angiotensin 1A receptors transfected into caudal ventrolateral medulla inhibit baroreflex gain and stress responses

作者：Palma Rigo Kesia; Bassi Jaspreet K; Thu Phuc Nguyen Huu; Jackson Kristy L; Davern Pamela J; Chen Daian; Elghozi Jean Luc; Thomas Walter G; Allen Andrew M; Head Geoffrey A^*

来源：Cardiovascular Research, 2012, 96(2): 330-339.

DOI：10.1093/cvr/cvs252

• Angiotensin type 1A receptor
• Caudal ventrolateral medulla
• Cardiovascular stress response
• Baroreflex gain

The caudal ventrolateral medulla (CVLM) is important for autonomic regulation and is rich in angiotensin II type 1A receptors (AT(1A)R). To determine their function, we examined whether the expression of AT(1A)R in the CVLM of micelacking AT(1A)R (AT(1A)(/)) alters baroreflex sensitivity and cardiovascular responses to stress. %26lt;br%26gt;Bilateral microinjections into the CVLM of AT(1A)(/) mice of lentivirus with the phox-2 selective promoter (PRSx8) were made to express either AT(1A)R (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 approximate to 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-AT(1A)- 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-AT(1A) mice compared with the control. %26lt;br%26gt;The expression of AT(1A)R 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.

• 出版日期2012-11-1