Elevated mitochondrial superoxide contributes to enhanced chemoreflex in heart failure rabbits.
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.
Ding
Yanfeng
Y
Dept. of Cellular and Integrative Physiology, Univ. of Nebraska Medical Center, Omaha, Nebraska 68198-5850, USA.
Li
Yu-Long
YL
Zimmerman
Matthew C
MC
Schultz
Harold D
HD
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002344:Carotid Body / Q000502:physiology; D005455:Fluorescent Antibody Technique; D018014:Gene Transfer Techniques; D006333:Heart Failure / Q000503:physiopathology*; D006334:Heart Function Tests; D007668:Kidney / Q000294:innervation / Q000502:physiology; D008297:Male; D008929:Mitochondria, Heart / Q000235:genetics / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D011817:Rabbits; D012018:Reflex / Q000235:genetics / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000502:physiology
D015221:Potassium Channels; D013481:Superoxides; D013482:Superoxide Dismutase