MRI assessment of coronary microvascular endothelial nitric oxide synthase function using myocardial T-1 mapping

作者：Cui Sophia X; Epstein Frederick H^*

来源：Magnetic Resonance in Medicine, 2018, 79(4): 2246-2253.

DOI：10.1002/mrm.26870

• T-1 mapping
• nitric oxide synthase inhibition
• coronary endothelial function
• microvascular permeability
• mouse
• eNOS

PurposeEndothelial nitric oxide synthase (eNOS) plays a central role in regulating vascular tone, blood flow, and microvascular permeability. Endothelial dysfunction, including eNOS dysfunction, is an early biomarker of vascular disease. This study aimed to show that myocardial T-1 mapping during nitric oxide synthase (NOS) inhibition could assess coronary microvascular eNOS function.
MethodsWild-type mice, eNOS(-/-) mice, and wild-type mice fed a high-fat diet underwent T-1 mapping at baseline and for 20min after injection of N-G-nitro-L-arginine methyl ester (LNAME), a NOS inhibitor. First-pass perfusion MRI was performed in wild-type mice at baseline and 5min after LNAME injection.
ResultsT(1) mapping detected an increase in myocardial T-1 5min after an injection of 4mg/kg LNAME compared with baseline in control mice (T-1=151530 ms with LNAME versus T-1=1402 +/- 30 ms at baseline, P<0.05). No change in myocardial T-1 after LNAME injection was observed in eNOS(-/-) mice. The change in T-1 after LNAME injection was less in high-fat-diet mice (T-1= 31 +/- 14 ms at 12 weeks of diet and T-1=16 +/- 17 ms at 18 weeks of diet) compared with mice fed a standard diet (T-1=113 +/- 15 ms), with P<0.05. First-pass MRI measured similar perfusion at baseline and 5min after LNAME injection.
ConclusionsNOS inhibition causes an increase in myocardial T-1 in healthy mice, and this effect is mediated through eNOS. T-1 mapping during NOS inhibition detects coronary microvascular eNOS dysfunction in high-fat-diet mice. T-1 mapping during NOS inhibition may be useful in preclinical studies aiming to investigate mechanisms underlying and therapies for coronary microvascular eNOS dysfunction. Magn Reson Med 79:2246-2253, 2018.

• 出版日期2018-4