Neuronal and Endothelial Nitric Oxide Synthases in the Paraventricular Nucleus Modulate Sympathetic Overdrive in Insulin-Resistant Rats

被引:7
作者
Lu, Qing-Bo [1 ]
Feng, Xue-Mei [2 ]
Tong, Ning [3 ]
Sun, Hai-Jian [1 ]
Ding, Lei [1 ]
Wang, Yu-Jiao [4 ]
Wang, Xuan [4 ]
Zhou, Ye-Bo [1 ]
机构
[1] Nanjing Med Univ, Dept Physiol, Key Lab Cardiovasc Dis & Mol Intervent, Nanjing 210029, Jiangsu, Peoples R China
[2] Luyi Peoples Hosp, Clin Lab, Zhoukou 466000, Peoples R China
[3] Heze Municipal Hosp, Dept Neurol, Heze 274000, Peoples R China
[4] Nanjing Med Univ, Clin Med Coll 4, Dept Pediat, Nanjing 210029, Jiangsu, Peoples R China
来源
PLOS ONE | 2015年 / 10卷 / 10期
基金
中国国家自然科学基金;
关键词
AFFERENT REFLEX; NERVOUS-SYSTEM; BLOOD-PRESSURE; ACTIVATION; HYPERTENSION; TETRAHYDROBIOPTERIN; HYPERINSULINEMIA; CONTRIBUTE; RECEPTORS; ESTROGEN;
D O I
10.1371/journal.pone.0140762
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A central mechanism participates in sympathetic overdrive during insulin resistance (IR). Nitric oxide synthase (NOS) and nitric oxide (NO) modulate sympathetic nerve activity (SNA) in the paraventricular nucleus (PVN), which influences the autonomic regulation of cardiovascular responses. The aim of this study was to explore whether the NO system in the PVN is involved in the modulation of SNA in fructose-induced IR rats. Control rats received ordinary drinking water, whereas IR rats received 12.5% fructose-containing drinking water for 12 wks to induce IR. Basal SNA was assessed based on the changes in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in response to chemicals administered to the PVN. We found an increased plasma norepinephrine level but significantly reduced NO content and neuronal NOS (nNOS) and endothelial NOS (eNOS) protein expression levels in the PVN of IR rats compared to Control rats. No difference in inducible NOS (iNOS) protein expression was observed between the two groups. In anesthetized rats, the microinjection of sodium nitroprusside (SNP), an NO donor, or N omega-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor of NOS, into the PVN significantly decreased and increased basal SNA, respectively, in both normal and IR rats, but these responses to SNP and L-NAME in IR rats were smaller than those in normal rats. The administration of selective inhibitors of nNOS or eNOS, but not iNOS, to the PVN significantly increased basal SNA in both groups, but these responses were also smaller in IR rats. Moreover, IR rats exhibited reduced nNOS and eNOS activity in the PVN. In conclusion, these data indicate that the decreased protein expression and activity levels of nNOS and eNOS in the PVN lead to a reduction in the NO content in the PVN, thereby contributing to a subsequent enhancement in sympathoexcitation during IR.
引用
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页数:18
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