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

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.

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 N^G -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.

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.

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. © 2017 International Society for Magnetic Resonance in Medicine.