<BOLD>Background</BOLD> Within cardiomyocytes, endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS) are thought to modulate L-type calcium channel (LTCC) function and sarcoplasmic reticulum calcium cycling, respectively. However, divergent results from mostly invasive prior studies suggest more complex roles. To elucidate the roles of nNOS and eNOS in vivo, we applied noninvasive cardiac MRI to study wild-type (WT), eNOS-/- and nNOS-/- mice. <BOLD>Methods and Results</BOLD> An in vivo index of LTCC flux (LTCCI) was measured at baseline (Bsl), dobutamine (Dob), and dobutamine+carbacholamine (Dob+CCh) using manganese-enhanced MRI. Displacement-encoded MRI assessed contractile function by measuring circumferential strain (Ecc), and systolic (dEcc/dt) and diastolic (dEcc/dtdiastolic) strain rates at Bsl, Dob, and Dob+CCh. Bsl LTCCI was highest in nNOS-/- mice (p<0.05 vs WT & eNOS-/-), and increased only in WT and eNOS-/- mice with Dob (p<0.05 vs. Bsl). LTCCI decreased significantly from Dob levels with Dob+CCh in all mice. Contractile function, as assessed by Ecc, was similar in all mice at Bsl. With Dob, Ecc increased significantly in WT and eNOS-/- but not nNOS-/- mice (p<0.05 vs. WT & eNOS-/-). With Dob+CCh, Ecc returned to baseline levels in all mice. Systolic blood pressure, measured via tail plethysmography, was highest in eNOS-/- mice (p<0.05 vs. WT & nNOS-/-). <BOLD>Conclusions</BOLD> Mice deficient in nNOS demonstrate increased Bsl LTCC function and an attenuated contractile reserve to Dob, while eNOS-/- mice demonstrate normal LTCC and contractile function under all conditions. These results suggest that nNOS, not eNOS, plays the dominant role in modulating Ca2+ cycling in the heart.
- Magnetic Resonance Imaging
- Nitric Oxide Synthase
- Contractile Function
- Copyright © 2011, American Journal of Physiology - Heart and Circulatory Physiology