The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase

TY - JOUR

T1 - The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase

AU - Khan, Sitara Gulurkh

AU - Melikian, Narbeh

AU - Shabeeh, Husain

AU - Cabaco, Ana Rita

AU - Martin, Katherine

AU - Khan, Faisal

AU - O'Gallagher, Kevin

AU - Chowienczyk, Phil

AU - Shah, Ajay M

N1 - Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology.

PY - 2017/6/23

Y1 - 2017/6/23

N2 - INTRODUCTION: Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental-stress-induced increases in coronary blood flow is unknown.METHODS: We studied eleven patients (6 men, mean age 58±14 years) undergoing elective diagnostic cardiac catheterization, and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intra-coronary substance P (20pmol/min) and isosorbide dinitrate (1mg) were used to assess endothelium-dependent and -independent vasodilation respectively. Coronary blood flow was estimated using intra-coronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter.RESULTS: Mental stress increased coronary flow by 34±7.0% over the preceding baseline during saline infusion (p<0.01), and this was reduced to 26±7.0% in the presence of the selective nNOS inhibitor S-methyl L-thiocitrulline (SMTC, 0.625µmol/min; p<0.001). Mental stress increased coronary artery diameter by 6.9±3.7% (p=0.02), and by 0.5±2.8% (p=0.51) in the presence of SMTC. The response to substance P did not predict the response to mental stress (r(2) = -0.22, p=0.83).CONCLUSION: nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels.

AB - INTRODUCTION: Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental-stress-induced increases in coronary blood flow is unknown.METHODS: We studied eleven patients (6 men, mean age 58±14 years) undergoing elective diagnostic cardiac catheterization, and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intra-coronary substance P (20pmol/min) and isosorbide dinitrate (1mg) were used to assess endothelium-dependent and -independent vasodilation respectively. Coronary blood flow was estimated using intra-coronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter.RESULTS: Mental stress increased coronary flow by 34±7.0% over the preceding baseline during saline infusion (p<0.01), and this was reduced to 26±7.0% in the presence of the selective nNOS inhibitor S-methyl L-thiocitrulline (SMTC, 0.625µmol/min; p<0.001). Mental stress increased coronary artery diameter by 6.9±3.7% (p=0.02), and by 0.5±2.8% (p=0.51) in the presence of SMTC. The response to substance P did not predict the response to mental stress (r(2) = -0.22, p=0.83).CONCLUSION: nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels.

U2 - 10.1152/ajpheart.00745.2016

DO - 10.1152/ajpheart.00745.2016

M3 - Article

C2 - 28646032

SN - 0363-6135

JO - AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY

JF - AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY

ER -