MRI assessment of coronary microvascular endothelial nitric oxide synthase function using myocardial T 1 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 T 1 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 T 1 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. Results T 1 mapping detected an increase in myocardial T 1 5 min after an injection of 4 mg/kg LNAME compared with baseline in control mice (T 1  = 1515 ± 30 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 (ΔT 1  = 31 ± 14 ms at 12 weeks of diet and ΔT 1  = 16 ± 17 ms at 18 weeks of diet) compared with mice fed a standard diet (ΔT 1  = 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 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. © 2017 International Society for Magnetic Resonance in Medicine.