Skeletal muscle microvascular oxygenation dynamics in heart failure: exercise training and nitric oxide-mediated function

Chronic heart failure (CHF) impairs nitric oxide (NO)-mediated regulation of skeletal muscle O-2 delivery-utilization matching such that microvascular oxygenation falls faster (i. e., speeds PO(2)mv kinetics) during increases in metabolic demand. Conversely, exercise training improves (slows) muscle PO(2)mv kinetics following contractions onset in healthy young individuals via NO-dependent mechanisms. We tested the hypothesis that exercise training would improve contracting muscle microvascular oxygenation in CHF rats partly via improved NO-mediated function. CHF rats (left ventricular end-diastolic pressure = 17 +/- 2 mmHg) were assigned to sedentary (n = 11) or progressive treadmill exercise training (n = 11; 5 days/ wk, 6 -8 wk, final workload of 60 min/day at 35 m/ min; - 14% grade downhill running) groups. PO(2)mv was measured via phosphorescence quenching in the spinotrapezius muscle at rest and during 1-Hz twitch contractions under control (KrebsHenseleit solution), sodium nitroprusside (SNP; NO donor; 300 mu M), and N-G-nitro-L-arginine methyl ester (L-NAME, nonspecific NO synthase blockade; 1.5 mM) superfusion conditions. Exercisetrained CHF rats had greater peak oxygen uptake and spinotrapezius muscle citrate synthase activity than their sedentary counterparts (p < 0.05 for both). The overall speed of the PO(2)mv fall during contractions (mean response time; MRT) was slowed markedly in trained compared with sedentary CHF rats (sedentary: 20.8 +/- 1.4, trained: 32.3 +/- 3.0 s; p < 0.05), and the effect was not abolished by L-NAME (sedentary: 16.8 +/- 1.5, trained: 31.0 +/- 3.4 s; p > 0.05). Relative to control, SNP increased MRT in both groups such that trained CHF rats had slower kinetics (sedentary: 43.0 +/- 6.8, trained: 55.5 +/- 7.8 s; p < 0.05). Improved NO-mediated function is not obligatory for training-induced improvements in skeletal muscle microvascular oxygenation (slowed PO(2)mv kinetics) following contractions onset in rats with CHF.