Altered Stress Responses in Rats with low Glial Angiotensinogen

Rats with low glial-derived angiotensinogen (ASrAogen) have higher AT1 receptors in subfornical organ and paraventericular nucleus, brain regions important in stress responses, compared to Sprague-Dawley (SD) rats at 48 and 68 weeks of age consistent with decreased tissue angiotensins (Ang). However, neuronal expression of Ang II and Ang-(1-7) in these nuclei is similar between strains. We measured systolic blood pressure (SBP) and baroreflex sensitivity (BRS; bradycardia in response to increase in pressure) in conscious 68 week old rats with intracerebroventricular (i.c.v.) cannulae. SBP averaged 151 mm Hg in SD and 122 mm Hg in ASrAogen rats, confirming their lower resting SBP (P < 0.05). When ASrAogen animals were handled for connection of i.c.v. catheters or when candesartan but not saline was given, there was an increase in heart rate (HR) and signs of arousal. There were no cardiovascular or behavioral changes in SD animals to either handling or i.c.v. injections. BRS was increased in SD rats after i.c.v. candesartan, but not saline, as previously reported. However, in ASrAogen animals there was a trend for decreased BRS after saline administration, consistent with the observed stress response, which is known to attenuate BRS. Thus, in the absence of glial-derived Ang peptides, intact neural pathways of the brain renin-angiotensin system important in stress responses are enhanced and associated with suppression of BRS.