Oral Presentation Neuropathophysiology - an ISH satellite 2012

Contribution of central AT1 receptors to neurogenic hypertension in Schlager BPH/2J mice (#31)

Kristy L Jackson 1 , Thu-Phuc Nguyen-Huu 1 , Pamela J Davern 1 , Geoffrey A Head 1
  1. Baker IDI, Melbourne, Vic, Australia

Background

Schlager BPH/2J mice are suggested to have neurogenic hypertension associated with an exaggerated pressor response to aversive stress. The brain renin-angiotensin system (RAS) is known to modulate blood pressure (BP) and the stress response. Thus the aim is to determine the contribution of brain RAS to the hypertension in BPH/2J mice.

Methods

BPH/2J and normotensive BPN/3J (n=7-9) mice were implanted with intracerebroventricular (ICV) cannula and radio-telemetry probes. Losartan (10μg/hr) was infused ICV and peripherally by minipump for one week, with recording of BP and restraint stress performed at the end of treatment.

Results

BPH/2J have higher average 24-hour BP than BPN/2J (125±3 vs. 101±1 mmHg) and a greater response to restraint stress (D39±1 vs. 30±1mmHg). ICV infusions of losartan caused a reduction in BP in BPH/2J (-12±2mmHg, P<0.001) but not in BPN/3J mice. Subcutaneous losartan caused a similar hypotensive effect in BPH/2J to ICV infusion but had no effect in BPN/3J. ICV losartan augmented the pressor response to restraint in BPH/2J mice by 33% (P<0.001).

Conclusions

These findings suggest that while there is a contribution of RAS to hypertension in BPH/2J mice compared with BPN/3J, the similar effects of ICV and systemic administration suggest that this may occur peripherally rather than centrally. However, the augmentation of the pressor response to stress by ICV losartan suggests that CNS RAS may in fact inhibit the response to stress independent of the hypertension.