Nitric oxide synthase type-1 modulates cardiomyocyte contractility and calcium handling: association with low intrinsic aerobic capacity

The neuronal isoform of nitric oxide synthase (NOS-1) may be an important regulator of cardiac contractility by modifying calcium release and uptake from sarcoplasmic reticulum. Our working hypothesis was that NOS-1 modulates cardiomyocyte contractility more markedly in rat lines with low versus high congenital aerobic fitness. Rats performed high-intensity interval treadmill running 5 days per week over 8 weeks; age-matched sedentary rats served as controls. At baseline before the training program, aerobic fitness measured as maximal oxygen uptake was 30% higher, and cardiomyocyte contractility measured as fractional shortening 42% higher in high than in low congenital aerobic fitness rats. Training markedly increased aerobic fitness as well as cardiomyocyte contractility, relaxation and corresponding changes in calcium transient in both lines. Selective inhibition of NOS-1 increased cardiomyocyte contractility (12–43%) and calcium transient amplitude (10–28%), prolonged time to 50% relengthening (13–52%) and time to 50% calcium decay (17–35%), in all groups. Interestingly, NOS-1-inhibition abolished the difference in systolic events between low and high congenital aerobic fitness whereas no such findings occurred in diastolic parameters. NOS-1-derived nitric oxide production is a modulator of cardiomyocyte contractile performance and calcium handling in rats. It accounts for some of the difference between rats with low versus high congenital aerobic fitness, whereas it contributes little during adaptation to exercise training.