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Superoxide Depression in the Rostral Ventrolateral Medulla Contributes to centrally Antihyper-tensive Action of Moxonidine

Superoxide Depression in the Rostral Ventrolateral Medulla C...

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中国生理学会第24届全国会员代表大会暨生理学学术大会

作者： Yangkai Wang Weizhong Wang Department of Physiology Second Military Medical University

BACKGROUND AND PURPOSE:It has been demonstrated that centrally antihypertensive action of moxonidine is resulted from activation of Imidazoline-1 receptor（I1R）in the rostral ventrolateral medulla（RVLM）.Increased superoxide in the RVLM contributes to high level of blood pressure and sympathetic outflow in *** objective of the present study was to determine the effect of moxonidine onproduction of superoxide in the RVLM of spontaneously hypertensive rat（SHR）.EXPERIMENTAL APPROACH Sixteen-week old SHR that received intracerebroventricular（icv,2 weeks）infusion of the tested agents was subjected to subsequent *** cardiovascular parameters including blood pressure,heart rate,and renal sympathetic nerve activity were monitored by Powerlab system（ADInstrument,Inc）.RVLM tissue was collected for assessment of protein and m RNA expression by western blotting and *** production of superoxide in the RVLM was measured using dihydroethidium fluorescence *** for moxonidine’s effect on superoxide was investigated by lentivirus infection in the *** RESULTS ICV infusion of moxonidine（20 nmol/day,2 weeks）produced a significant decrease in BP（143±3 vs 186±5 mm Hg）in SHR,which can be prevented by the I1R antagonist efaroxan but not the alpha 2 receptor antagonist *** production of ROS in the RVLM was significantly reduced by an average of 37%in the SHR with moxonidine infusion compared with vehicle *** significantly blunted the decrease and increase in BP,HR,and RSNA evoked by injection of the SOD mimic Tempol（5 nmol）and Angiotensin Ⅱ（20 pmol）into the RVLM,*** expression of NADPHase（NOX4）and angiotensin type I receptor（AT1R）in the RVLM was significantly decreased in SHR with infusion of moxonidine.B ***?Moxonidine also significantly inactivated the PI3K-Akt-NF of lentivirus containing PI3K sh RNA in the RVLM effectively prevented effects of *** AND?moxonidine on BP

关键词： centrally antihypertensive mechanism superoxide PI3K rostral ventrolateral medulla

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