Abstract
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. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. 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 (0.625 µmol/min, P < 0.001). Mental stress increased coronary artery diameter by 6.9 ± 3.7% (P = 0.02) and 0.5 ± 2.8% (P = 0.51) in the presence of S-methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress (r2 = -0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels.NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/.
Highlights
NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature
Studies using intra-arterial infusion of a selective neuronal nitric oxide (NO) synthase inhibitor show that local nNOS-derived NO is a major contributor to the basal regulation of microvascular tone and blood flow in the human forearm and coronary circulations [32, 33]
We investigated the role of nNOS in the changes in coronary blood flow during acute mental stress in humans
Summary
NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. We show that this response involves neuronal nitric oxide synthase in the human coronary circulation. It was generally assumed that the NO responsible for mediating local increases in blood flow was generated by endothelial NO synthase (eNOS) expressed in endothelial cells [10, 16]. Studies using intra-arterial infusion of a selective neuronal NO synthase (nNOS) inhibitor show that local nNOS-derived NO is a major contributor to the basal regulation of microvascular tone and blood flow in the human forearm and coronary circulations [32, 33]. It was found that local nNOS is involved in mental stress-induced forearm vasodilatation in healthy humans. We investigated the role of nNOS in the changes in coronary blood flow during acute mental stress in humans
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