MRI assessment of coronary microvascular endothelial nitric oxide synthase function using myocardial T1 mapping.

PURPOSE: Endothelial 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 T1 mapping during nitric oxide synthase (NOS) inhibition could assess coronary microvascular eNOS function.
METHODS: Wild-type mice, eNOS-/- mice, and wild-type mice fed a high-fat diet underwent T1 mapping at baseline and for 20 min after injection of NG -nitro-L-arginine methyl ester (LNAME), a NOS inhibitor. First-pass perfusion MRI was performed in wild-type mice at baseline and 5 min after LNAME injection.
RESULTS: T1 mapping detected an increase in myocardial T1 5 min after an injection of 4 mg/kg LNAME compared with baseline in control mice (T1  = 1515 ± 30 ms with LNAME versus T1  = 1402 ± 30 ms at baseline, P < 0.05). No change in myocardial T1 after LNAME injection was observed in eNOS-/- mice. The change in T1 after LNAME injection was less in high-fat-diet mice (ΔT1  = 31 ± 14 ms at 12 weeks of diet and ΔT1  = 16 ± 17 ms at 18 weeks of diet) compared with mice fed a standard diet (ΔT1  = 113 ± 15 ms), with P < 0.05. First-pass MRI measured similar perfusion at baseline and 5 min after LNAME injection.
CONCLUSIONS: NOS inhibition causes an increase in myocardial T1 in healthy mice, and this effect is mediated through eNOS. T1 mapping during NOS inhibition detects coronary microvascular eNOS dysfunction in high-fat-diet mice. T1 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.