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.
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).
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).
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.
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aNeuropharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne
bDepartment of Pharmacology, Monash University, Clayton, Victoria, Australia
*P.J.D. and G.A.H. are joint senior authors for this publication.
Correspondence to Geoffrey A. Head, Neuropharmacology Laboratory, Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne 8008, AustraliaTel: +61 3 8532 1330; fax: +61 3 8532 1100; e-mail: firstname.lastname@example.org
Abbreviations: BP, blood pressure; BPH/2J, blood pressure high mice; BPN/3J, blood pressure normal mice; CNS, central nervous system; DAP, diastolic arterial pressure; HR, heart rate; ICV, intracerebroventricular; MAP, mean arterial pressure; PVN, paraventricular nucleus; ROR, rate of rise; RVLM, rostroventrolateral medulla; SAP, systolic arterial pressure; SHR, spontaneously hypertensive rats; SNS, sympathetic nervous system
Received 24 May, 2012
Accepted 30 September, 2013
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