Abstract 821: A Critical Role for Neuronal Nitric Oxide Synthase in the Physiologic Response to Exercise
Introduction: Neuronal nitric oxide synthase (nNOS) plays important roles in neurotransmission and in cardiac and peripheral muscle. We hypothesized that targeted deletion of the nNOS gene would lead to impaired exercise performance and altered cardiovascular response to chronic exercise training.
Methods: nNOS knockout mice (nNOS-KO) and Wild type (WT) littermates were singly housed in cages containing either freely rotating running wheels or fixed wheels. Exercise performance was analyzed by wheel rotations; heart rate and blood pressure were monitored continuously, using implantable telemeters.
Results: nNOS-KO mice ran the same number of bouts each night at the same speed as WT mice but covered significantly less distance (nNOS-KO 2.5 ± 0.3 km, WT 5.3 ± 0.8 km, p=0.002), due to a significant reduction in bout duration nNOS-KO mice (Panel A). Despite reduced exercise performance,,significant left ventricular hypertrophy was induced by exercise in nNOS-KO mice (12% increase, p=0.008), but not WT mice (5%, p=NS). At rest, untrained nNOS-KO mice were bradycardic compared to WT mice (Panel B), but this difference was abolished by 6 weeks wheel running. Furthermore, heart rate recovery after exercise was significantly reduced in nNOS-KO mice.
Conclusions: nNOS plays a critical physiological role in the hemodynamic and cardiac response to exercise training. Absence of nNOS prevents the development of the normal cardiac autonomic response to chronic exercise training despite the development of significant physiological hypertrophy