| Background: Heart failure (HF) is characterized by increased sympathetic nerve activity. The present study was undertaken to investigate the mechanism of oxidative stress in the paraventricular nucleus of hypothalamus (PVN) in the pathophysiology of HF.Methods: Adult male Sprague–Dawley (SD) rats (250-300g) were randomly divided into heart failure (HF) and control groups. Rats underwent coronary artery ligation to induce heart failure (HF), or sham operated surgery (SHAM). Two days later, rats were implanted with intracerebroventricular (ICV) cannulae and treated with tempol (80μg/kg/h), a superoxide scavenger, or vehicle (VEH,0.25μl/hr) for 4 weeks. After 4 weeks treatment, they were anesthetized for hemodynamic measurements and renal sympathetic nerve activity (RSNA) recording. Examines hypothalamic oxidation stress indicator of MDA, SOD, T-AOC with the biochemistry method. Brain samples were collected for measurement of the expression of gp91phox in the PVN by immunofluorescence and western blot. Heart and lung tissues were also harvested, wet lung weight and right ventricular (RV) weight, with respect to body weight (BW), were also measured.Results: 1. Right ventricle/body weight and wet lung/body weight: Heart failure group compared with the sham-operated group, RVW / BW and lung / BW was significantly higher (P<0.05), given after tempol, rats with heart failure RVW / BW and lung / BW lower (P<0.05), but higher than in SHAM group level (P<0.05); 2. Hemodynamic mesurements: Mean arterial pressure (MAP) of rats in every group is non-discrimination; heart failure group compared with the sham-operated group, left ventricular systolic pressure (LVSP), left ventricular pressure rise rate of the maximum (LV + dp / dtmax) and left ventricular pressure maximum decline rate (LV-dp/dtmax) lower (P<0.05), left ventricular end diastolic pressure (LVEDP) increased (P<0.05), the difference was statistically significant; and after the intervention of tempol, the indicators are to some extent improved; but there are still differences compare with SHAM group (P<0.05); 3. Renal sympathetic nerve activity: Heart failure group compared with the sham-operated group, renal sympathetic nerve activity increased significantly (P<0.05), given after tempol, renal sympathetic nerve activity (P<0.05); but higher than the level of SHAM group (P<0.05); 4. Immunohistochemistry: Sham-operated rats hypothalamic paraventricular nucleus in the expression of NADPH subunit gp91phox negative, heart failure in rats with paraventricular nucleus NADPH subunit gp91phox expression (P<0.05). Heart failure in rats after intervention by tempol hypothalamic paraventricular nucleus in the expression of NADPH subunit gp91phox reduced, but more than sham-operated group (P<0.05); 5. Western blotting: Heart failure group compared with the sham-operated group, hypothalamic paraventricular nucleus increase gp91phox expression (P<0.05), after tempol given, gp91phox expression reduction (P<0.05), but still higher than sham-operated group; 6. Oxidized stress indicator examination: Heart failure group compared the sham-operated group, T-AOC,SOD activity is decrease and MDA is increase in hypothalamic paraventricular nucleus(P<0.05), after tempol given, T-AOC,SOD activity increase, MDA decrease(P<0.05), but still lower than sham-operated group.Conclusion: These findings suggest that oxidative stress in the PVN induces the sympathoexcitation at contribute to the pathogenesis of heart failure, and ICV treatment with tempol decrease the brain level of oxygen free radical attenuates cardiac dysfunction. |
PDF Full Text Request