Oxidative stress in carotid body contributes to enhanced chemoreflex in heart failure: focus on "Elevated mitochondrial superoxide contributes to enhanced chemoreflex in heart failure rabbits".
نویسندگان
چکیده
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.
منابع مشابه
Editorial Focus. Oxidative stress in carotid body contributes to enhanced chemoreflex in heart failure: focus on mitochondrial superoxide anion
متن کامل
Elevated mitochondrial superoxide contributes to enhanced chemoreflex in heart failure rabbits
Ding Y, Li Y, Zimmerman MC, Schultz HD. Elevated mitochondrial superoxide contributes to enhanced chemoreflex in heart failure rabbits. Am J Physiol Regul Integr Comp Physiol 298: R303–R311, 2010. First published November 18, 2009; doi:10.1152/ajpregu.00629.2009.—Peripheral chemoreflex sensitivity is enhanced in both clinical and experimental chronic heart failure (CHF). Here we investigated th...
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The present study aimed to determine whether peripheral and/or central chemoreflex function is altered in chronic heart failure (CHF) and whether altered chemoreflex function contributes to sympathetic activation in CHF. A rabbit model of pacing-induced CHF was employed. The development of CHF (3-4 wk of pacing) was characterized by an enlarged heart, an attenuated contractility, and an elevate...
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ورودعنوان ژورنال:
- American journal of physiology. Regulatory, integrative and comparative physiology
دوره 298 2 شماره
صفحات -
تاریخ انتشار 2010