Oxidative stress and the muscle reflex in heart failure.
Muscle contraction stimulates thin fibre muscle afferents and evokes a reflex increase in blood pressure. In heart failure (HF) this reflex is accentuated. Of note, superoxide and other reactive oxygen species are increased in HF. In this report, we tested the hypothesis that excess superoxide contributes to the exaggerated muscle reflex in HF. HF was induced in rats by coronary artery ligation. Electrically induced 30 s hindlimb muscle contraction in decerebrate rats with myocardial infarction (MI) (left ventricular fractional shortening (FS) = 24 +/- 1%; n = 15) evoked larger (P < 0.05) increases in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) as compared to control rats (FS = 47 +/- 1%; n = 14). In the MI rats, the pressor and RSNA responses to contraction were reduced by intra-arterial injection into the hindlimb circulation of tempol (10 mg), a superoxide dismutase mimetic (DeltaMAP: 22 +/- 2 vs. 11 +/- 1 mmHg; integral DeltaRSNA: 1032 +/- 204 vs. 431 +/- 73 arbitrary units (a.u.); before vs. after tempol; P < 0.05). Tempol also attenuated the RSNA response to 1 min intermittent (1-4 s stimulation to relaxation) bouts of static contraction in the MI rats (116 +/- 17 vs. 72 +/- 11 a.u.; P < 0.05; n = 16). In the control rats, tempol had no effect on these responses. These results suggest that excess superoxide in HF sensitizes mechanically sensitive muscle afferents engaged during contraction. We hypothesize that oxidative stress contributes to the exaggerated muscle reflex in HF.
Koba
Satoshi
S
Penn State Heart and Vascular Institute, Pennsylvania State University College of Medicine, 500 University Dr, Hershey, PA 17033, USA. skoba@med.tottori-u.ac.jp.
Gao
Zhaohui
Z
Sinoway
Lawrence I
LI
D000818:Animals; D006333:Heart Failure / Q000503:physiopathology*; D006614:Hindlimb / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000294:innervation* / Q000503:physiopathology*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex