Importance of the medial amygdala to the neurogenic hypertension in Schlager mice

Schlager mice are hypertensive due to an overactive sympathetic nervous system, which is associated with a greater blood pressure (BP) reactivity to stress. The medial amygdala (MeAm) is a major site within the forebrain, integrating the autonomic responses to stress. Interestingly this region was also found to have the highest correlation with blood pressure levels in Schlager mice. To determine whether the MeAm could be responsible for the hypertension, we assessed the effect of MeAm ablation on BP and stress reactivity. Radio-telemetry devices were implanted in 10 normotensive (BPN) and 8 hypertensive (BPH) mice. Two weeks later, ibotenic acid was injected bilaterally into the MeAm to lesion this region. In the week before and 3 weeks after lesion surgery, cardiovascular parameters were measured for 48 hrs and a series of stress tests were performed. During control measurements, BP was 121±4 mmHg in BPH compared to 101±2 mmHg in BPN mice (P<0.0001). MeAm lesions had no effect on the locomotor activity patterns in either strain but caused a marked reduction in 24 hr BP, -11±5 mmHg (P=0.005) in BPH mice and no effect in BPN mice. The effect of the lesions was similar during both day and night, suggesting a tonic effect independent of circadian rhythm. Despite the marked reduction in blood pressure in BPH mice, the pressor response to restraint stress was well maintained in BPH lesion mice. Further, the pressor response to cage change was greater than prior to lesions in BPH mice (P=0.02). These results clearly show that the MeAm is crucial for the hypertension in Schlager BPH mice, providing a tonic activation, which seems to be independent of its role in stress reactivity or circadian BP influences.