Low dose of moxonidine within the rostral rentrolateral medulla improves the baroreflex ;ensitivity control of sympathetic activity in hypertensive rat  

作　　者：Jia-ling WANG Long WANG Zhao-tang WU Wen-jun YUAN Ding-feng SU Xin NI Jian-jun YAN Wei-zhong WANG 

机构地区：[1]Department of Physiology Second Military Medical University, Shanghai 200433, China [2]Department of Emergency, Changhai Hospital, Shanghai 200433, China [3]Shanghai Research Center for Biomodel Organism, Shanghai 200433, China [4]Department of Pharmacology, Second Military Medical University, Shanghai 200433, China [5]The First Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200433, China

出　　处：《Acta Pharmacologica Sinica》2009年第12期1594-1600,共7页中国药理学报（英文版）

基　　金：Acknowledgements 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 Shang hai （No 06QB14029 and 09PJ1400100）.

摘　　要：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.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.

关 键 词：centrally-acting drug I1-imidazoline receptor MICROINJECTION extracellular recording presympathetic neuron 

分 类 号：Q463[生物学—生理学] Q425