Background: Schlager BPH/2J hypertensive mice have high blood pressure likely due to overactivity of the sympathetic nervous system regulated by neurons in amygdala-hypothalamic pathways. These areas are normally under tonic inhibition by GABA containing neurons that may be deficient in Schlager hypertensive mice as suggested by microarray analysis.
Methods: Cardiovascular effects of chronic activation of GABAA receptors were examined in male normotensive BPN/3J and BPH/2J mice administered diazepam in drinking water for 7 days. Blood pressure, heart rate and locomotor activity were recorded by telemetry.
Results: Diazepam (2.5mg/kg) reduced blood pressure of BPN/3J mice during the night time by -7.1±2.0mmHg (P=0.001) but had no effect in BPH/2J mice (+2±2mmHg) and no effect on heart rate or locomotor activity in either strain. Diazepam reduced the responses to restraint stress in BPN/3J mice by 20% (P=0.03) and eliminated Fos-immunoreactive neurons expressing GABAA receptors or Neuropeptide Y in the medial amygdala and paraventricular nucleus of the hypothalamus. By contrast diazepam had no effect on the pressor response to stress in BPH/2J mice and ~70% of stress activated neurons in these regions also expressed GABAA receptors and were neuropeptide Y-containing.
Conclusions: These findings show that BPH/2J mice are resistant to the effects of diazepam and suggests that GABAA receptor dysfunction in BPH/2J mice may be contributing to the neurogenic hypertension by not suppressing arousal induced sympathetic activation within amygdala and hypothalamic nuclei.
Disclosure: none.