Increased central reactive oxygen species mediate the attenuated baroreflex function in heart failure |
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| Authors: | PAN Yan-xia WANG Wei |
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| Institution: | 1.Department of Physiology and Pathophysiology, Basic Medical College, Fujian Medical University, Fuzhou 350004, China;2.Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha NE68198-5850, USA. E-mail: ypan266@sina.com |
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| Abstract: | AIM: To determine the effect of reactive oxygen species on the baroreflex and to investigate the intracellular mechanism responsible for baroreflex dysfunction in the heart failure state.METHODS: In the rat model of cardiomyocytes infarct induced heart failure, baroreflex function was evaluated by measuring the relationship between renal sympathetic nerve activity(RSNA)responses and change of blood pressure by intravenous injection of nitroglycerin and phenylephrine. Alteration in baroreflex function was measured under the different reactive oxygen species(ROS)level induced by intracerebroventricular administration of several chemicals. RESULTS: (1)The range of RSNA response, average slope and maximum gain of baroreflex function curve were(92.2±9.9) mmHg,(0.07%±0.01%)/mmHg and(1.20%±0.10%)/mmHg, respectively, in CHF rats, which were significantly lower than those in sham rats(65.6±7.4) mmHg,(0.13%±0.02%)/mmHg and(3.00%± 0.20%)/mmHg(P<0.01).The minimum RSNA of baroreflex curve was higher in CHF rats than that in sham rat［(21.6%±4.8%)vs(7.5%±2.1%), P<0.01］.(2)Intracerebroventricular(icv)infusion of superoxide scavenger tempol and NADPH oxidase inhibitor apocynin significantly improved the blunted baroreflex in CHF rats. On contrast, icv administration of superoxide dismutase inhibitor diethyldithiocarbamate(DETC)decreased baroreflex function in sham rats.(3)The superoxide production in the hypothalamus of CHF rats was higher than that in sham rats［(73.9±9.8)RLU·5min-1·mg-1vs(40.6±7.1)RLU·5min-1·mg-1, P<0.01］.(4)Protein expression of NADPH oxidase subunits gp91phox in the paraventricular nucleus of the hypothalamus were increased by 1.3 fold in CHF rats than that in sham rats. CONCLUSION: Elevated intracellular ROS in the hypothalamus plays an important role in the attenuation of baroreflex function in the heart failure state and results from upregulation of NADPH oxidase protein expression. |
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