Dept. of Cellular and Integrative Physiology, Univ. of Nebraska Medical Center, Omaha, Nebraska 68198-5850, USA.
Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R303-11. doi: 10.1152/ajpregu.00629.2009. Epub 2009 Nov 18.
Peripheral chemoreflex sensitivity is enhanced in both clinical and experimental chronic heart failure (CHF). Here we investigated the role of manganese superoxide dismutase (MnSOD), the SOD isoform specially targeted to mitochondria, and mitochondrial superoxide levels in the enhanced chemoreceptor activity and function of the carotid body (CB) in CHF rabbits. CHF suppressed MnSOD protein expression and elevated mitochondrial superoxide levels in CB compared with that in sham CB. Adenovirus (Ad) MnSOD (1 x 10(8) plaque-forming units/ml) gene transfer selectively to the CBs normalized mitochondrial superoxide levels in glomus cells from CHF CB. In addition, Ad MnSOD reduced the elevation of superoxide level in CB tissue from CHF rabbits. Ad MnSOD significantly increased MnSOD expression in CHF CBs and normalized the baseline renal sympathetic nerve activity and the response of renal sympathetic nerve activity to hypoxia in CHF rabbits. Ad MnSOD decreased baseline single-fiber discharge from CB chemoreceptors compared with Ad Empty (6.3 + or - 1.5 vs. 12.7 + or - 1.4 imp/s at approximately 100-Torr Po(2), P < 0.05) and in response to hypoxia (20.5 + or - 1.8 vs. 32.6 + or - 1.4 imp/s at approximately 40-Torr Po(2), P < 0.05) in CHF rabbits. Compared with Ad Empty, Ad MnSOD reversed the blunted K(+) currents in CB glomus cells from CHF rabbits (385 + or - 11 vs. 551 + or - 20 pA/pF at +70 mV, P < 0.05). The results suggest that decreased MnSOD in the CB and elevated mitochondrial superoxide levels contribute to the enhanced CB chemoreceptor activity and peripheral chemoreflex function in CHF rabbits.
外周化学感受器敏感性在临床和实验性慢性心力衰竭 (CHF) 中均增强。在这里，我们研究了锰超氧化物歧化酶 (MnSOD) 的作用，MnSOD 是专门针对线粒体的 SOD 同工酶，以及线粒体中超氧阴离子水平在 CHF 兔颈动脉体 (CB) 化学感受器活性和功能增强中的作用。CHF 抑制了 CB 中的 MnSOD 蛋白表达，并增加了线粒体中超氧阴离子的水平，与 sham CB 相比。腺病毒 (Ad) MnSOD(1x10(8) 噬菌斑形成单位/ml)基因转染到 CB 中可使 CHF CB 中的颗粒细胞中线粒体中超氧阴离子水平正常化。此外，Ad MnSOD 降低了 CHF 兔 CB 组织中超氧阴离子水平的升高。Ad MnSOD 显著增加了 CHF CB 中的 MnSOD 表达，并使 CHF 兔的基础肾交感神经活动和肾交感神经活动对缺氧的反应正常化。与 Ad Empty 相比，Ad MnSOD 降低了 CHF 兔 CB 化学感受器的基线单纤维放电，从 CB 化学感受器的基线单纤维放电 (在大约 100-Torr Po(2) 时为 6.3+/-1.5 与 12.7+/-1.4imp/s，P<0.05) 和对缺氧的反应 (在大约 40-Torr Po(2) 时为 20.5+/-1.8 与 32.6+/-1.4imp/s，P<0.05)。与 Ad Empty 相比，Ad MnSOD 逆转了 CHF 兔 CB 颗粒细胞中钾电流的减弱 (在+70 mV 时为 385+/-11 与 551+/-20 pA/pF，P<0.05)。结果表明，CB 中 MnSOD 的减少和线粒体中超氧阴离子水平的升高导致 CHF 兔 CB 化学感受器活性和外周化学反射功能增强。
