Displacement-encoded and manganese-enhanced cardiac MRI reveal that nNOS, not eNOS, plays a dominant role in modulating contraction and calcium influx in the mammalian heart

作者：Vand**urger Moriel H; French Brent A; Kramer Christopher M; Zhong Xiaodong; Epstein Frederick H^*

来源：American Journal of Physiology - Heart and Circulatory Physiology, 2012, 302(2): H412-H419.

DOI：10.1152/ajpheart.00705.2011

• magnetic resonance imaging
• endothelial nitric oxide synthase
• neuronal nitric oxide synthase
• contractile function

Vandsburger MH, French BA, Kramer CM, Zhong X, Epstein FH. Displacement-encoded and manganese-enhanced cardiac MRI reveal that nNOS, not eNOS, plays a dominant role in modulating contraction and calcium influx in the mammalian heart. Am J Physiol Heart Circ Physiol 302: H412-H419, 2012. First published November 4, 2011; doi:10.1152/ajpheart.00705.2011.-Within cardiomyocytes, endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (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. 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 (dE(cc/)dt) and diastolic (dE(cc)/dt(diastolic)) strain rates at Bsl, Dob, and Dob + CCh. Bsl LTCCI was highest in nNOS(-/-) mice (P < 0.05 vs. WT and 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 and 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 and nNOS(-/-)). Mice deficient in nNOS demonstrate increased Bsl LTCC function and an attenuated contractile reserve to Dob, whereas 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.

• 出版日期2012-1