Fig. 5: Exercise capacity is reduced with total loss of function, but not with eNOS binding disruption.

a Schematic of the exercise capacity protocol. After an initial blood sample was collected for baseline lactate measurement, mice were encouraged to run on a treadmill until exhaustion. The treadmill speed was increased every 30 min until a maximum speed of 26.8 m/min (1 mile per hour) was achieved. After running failure, a second blood sample was taken to monitor lactate buildup and thereby ensure physical exhaustion. b Body weight measurements for Hba1^fl/fl vs. EC Hba1^Δ/Δ or for the Hba1^WT/WT vs. Hba1^WT/Δ36–39 littermate groups did not differ. c The distance to exhaustion was shorter in EC Hba1^Δ/Δ mice compared to Hba1^fl/fl littermates; no such difference was observed when the distances to exhaustion for the Hba1^WT/WT and Hba1^WT/Δ36–39 littermate groups were compared. d Blood lactate was increased in all groups after exercise, but no differences were observed between the control and experimental groups. e Soleus muscle capillary density was similar across littermate comparisons. For the experiments in b–d, n = 23 for Hba1^fl/fl mice; n = 26 for EC Hba1^Δ/Δ mice; n = 13 for Hba1^WT/WTmice; and n = 11 Hba1^WT/Δ36–39 mice were used. For the experiments in e, n = 6 for Hba1^fl/fl mice; n = 6 for EC Hba1^Δ/Δ mice; n = 5 for Hba1^WT/WT mice; and n = 3 for Hba1^WT/Δ36–39 mice were used. Results for different littermate genotypes were compared with t tests. Bar graphs are centered on mean with error bars denoting standard error. Source data are provided in the Source data file.