Acta Pharmacologica Sinica (2009) 30: 1594–1600; doi: 10.1038/aps.2009.165

Acta Pharmacologica Sinica (2009) 30: 1594–1600; doi: 10.1038/aps.2009.165

Original Article

Low dose of moxonidine within the rostral ventrolateral medulla improves the baroreflex sensitivity control of sympathetic activity in hypertensive rat

Jia-ling WANG^{1, 2, #}, Long WANG^{3, #}, Zhao-tang WU^{4,
#}, Wen-jun YUAN¹, Ding-feng SU⁴, Xin NI¹, Jian-jun YAN^5,*, Wei-zhong WANG^1,*

Department of ¹Physiology and ⁴Pharmacology, Second Military Medical University, Shanghai 200433, China; ²Department of Emergency, Changhai Hospital, Shanghai 200433, China; ³Shanghai Research Center for Biomodel Organism, Shanghai 200433, China; ⁵The First Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200433, China

Aim: To determine the effects of the centrally antihypertensive drug moxonidine injected into the rostral ventrolateral medulla (RVLM) on baroreflex function in spontaneously hypertensive rats (SHR).

Methods: Baroreflex sensitivity control of renal sympathetic nerve activity (RSNA) and barosensitivity of the RVLM presympathetic neurons were determined following application of different doses of moxonidine within the RVLM.

Results: Three doses (0.05, 0.5, and 5 nmol in 50 nL) of moxonidine injected bilaterally into the RVLM dose-dependently reduced the baseline blood pressure (BP) and RSNA in SHR. At the highest dose (5 nmol) of moxonidine injection, the maximum gain (1.24%±0.04%/mmHg) of baroreflex control of RSNA was significantly decreased. However, the lower doses (0.05 and 0.5 nmol) of moxonidine injection into the RVLM significantly enhanced the baroreflex gain (2.34%±0.08% and 2.01%±0.07%/mmHg). The moxonidine-induced enhancement in baroreflex function was completely prevented by the imidazoline receptor antagonist efaroxan but not by the α₂-adrenoceptor antagonist yohimbine. A total of 48 presympathetic neurons were recorded extracellularly in the RVLM of SHR. Iontophoresis of applied moxonidine (30–60 nA) dose-dependently decreased the discharge of RVLM presympathetic neurons but also significantly increased the barosensitivity of RVLM presympathetic neurons.

Conclusion: These data demonstrate that a low dose of moxonidine within the RVLM has a beneficial effect on improving the baroreflex function in SHR via an imidazoline receptor-dependent mechanism.

Keywords: centrally-acting drug; I₁-imidazoline receptor; microinjection; extracellular recording; presympathetic neuron

This work was supported by the National Natural Science Foundation of China (No 30670759 and 30971061) and the Major State Basic Research Development Program of China (No 2006CB503807). This work was also supported by the grant from the Science and Technology Commission of Shanghai (No 06QB14029 and 09PJ1400100).

^#These authors equally contribute to this work.
* To whom correspondence should be addressed.
E-mail wangwz68@hotmail.com(Wei-zhong WANG); rian1971@sina.com (Jian-jun YAN)
Received 2009-07-22 Accepted 2009-10-19

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