Actions of rilmenidine on neurogenic hypertension in BPH/2J genetically hypertensive mice

作者：Jackson Kristy L; Palma Rigo Kesia; Thu Phuc Nguyen Huu; Davern Pamela J; Head Geoffrey A^*

来源：Journal of Hypertension, 2014, 32(3): 575-586.

DOI：10.1097/HJH.0000000000000036

• BPH/2J mice
• hypertension
• rilmenidine
• rostroventrolateral medulla
• sympathetic nervous system

Objective:
BPH/2J hypertensive mice have an exaggerated sympathetic contribution to blood pressure (BP). Premotor sympathetic neurons within the rostroventrolateral medulla (RVLM) are a major source of sympathetic vasomotor tone and major site of action of the centrally acting sympatholytic agent, rilmenidine. The relative cardiovascular effect of rilmenidine in BPH/2J versus normotensive BPN/3J mice was used as an indicator of the involvement of the RVLM in the sympathetic contribution to hypertension in BPH/2J mice.
Methods:
BPH/2J and BPN/3J mice were pre-implanted with telemetry devices to measure BP in conscious unrestrained mice. Rilmenidine was administered acutely (n=7-9/group), orally for 14 days, at a wide range of doses (n=5/group), and also infused intracerebroventricularly for 7 days (n=6/group).
Results:
Acute intraperitoneal rilmenidine induced greater depressor and bradycardic responses in BPH/2J than BPN/3J mice (P-strain<0.01). Both responses were reduced by atropine pre-treatment, with the remaining hypotensive effect being small and comparable between strains (P-strain=1.0). This suggests that vagally induced reductions in cardiac output were responsible for the hypotension. Chronic intracerebroventricularly infused rilmenidine reduced BP from baseline marginally in BPH/2J mice during the dark (active) period (-6.5 +/- 2 mmHg; P=0.006). Chronic orally administered rilmenidine (1-12 mg/kg per day) also had minimal effect on 24-h BP in both strains (P>0.16).
Conclusion:
The sympathetic vasomotor inhibitory effect of rilmenidine is minimal in both strains and similar in hypertensive BPH/2J and BPN/3J mice. Thus, hypertension in BPH/2J mice is not likely mediated by greater neuronal activity in the RVLM, and agents such as rilmenidine would be an ineffective treatment for this form of neurogenic hypertension.

• 出版日期2014-3