Nitroglycerine-Induced Vasodilation for Assessment of Vascular Function: A Comparison With Flow-Mediated Vasodilation

Objective—Nitroglycerine-induced vasodilation has been used as a control test for flow-mediated vasodilation (FMD) to differentiate endothelium-dependent from endothelium-independent response when evaluating endothelial function in humans. Recently, nitroglycerine-induced vasodilation has also been reported to be impaired in patients with atherosclerosis. The purpose of this study was to determine the relationships between nitroglycerine-induced vasodilation and cardiovascular risk factors. Approach and Results—We measured nitroglycerine-induced vasodilation and FMD in 436 subjects who underwent health examinations (mean age, 53±19 years; age range, 19–86 years), including patients with cardiovascular diseases. There was a significant relationship between nitroglycerine-induced vasodilation and FMD (r=0.42; P<0.001). Univariate regression analysis revealed that nitroglycerine-induced vasodilation correlated with age (r=−0.34; P<0.001), systolic blood pressure (r=−0.32; P<0.001), diastolic blood pressure (r=−0.24; P<0.001), heart rate (r=−0.21; P<0.001), glucose (r=−0.23; P<0.001), and smoking pack-year (r=−0.12; P=0.01), as well as Framingham risk score (r=−0.30; P<0.001). Nitroglycerine-induced vasodilation was significantly smaller in patients with cardiovascular disease than in both subjects with and without cardiovascular risk factors (10.5±5.6% versus 13.7±5.4% and 15.3±4.3%; P<0.001, respectively), whereas there was no significant difference in nitroglycerine-induced vasodilation between subjects with and without cardiovascular risk factors. Multivariate analysis revealed that male sex, body mass index, hypertension, diabetes mellitus, baseline brachial artery diameter, and FMD were independent predictors of nitroglycerine-induced vasodilation. Conclusions—These findings suggest that nitroglycerine-induced vasodilation may be a marker of the grade of atherosclerosis. FMD should be interpreted as an index of vascular function reflecting both endothelium-dependent vasodilation and endothelium-independent vasodilation in subjects with impaired nitroglycerine-induced vasodilation.

[1]  A. Nakashima,et al.  Hyperbilirubinemia, Augmentation of Endothelial Function, and Decrease in Oxidative Stress in Gilbert Syndrome , 2012, Circulation.

[2]  HirofumiTomiyama,et al.  Hyperbilirubinemia, Augmentation of Endothelial Function, and Decrease in Oxidative Stress in Gilbert Syndrome , 2012 .

[3]  Yukihito Higashi,et al.  Rho-Associated Kinase Activity, Endothelial Function, and Cardiovascular Risk Factors , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[4]  H. Arima,et al.  Differential effects of organic nitrates on arterial diameter among healthy Japanese participants with different mitochondrial aldehyde dehydrogenase 2 genotypes: randomised crossover trial , 2011, BMJ Open.

[5]  K. Chayama,et al.  Vascular Function and Circulating Progenitor Cells in Thromboangitis Obliterans (Buerger's Disease) and Atherosclerosis Obliterans , 2011, Hypertension.

[6]  David M. Herrington,et al.  Predictive Value of Brachial Flow-Mediated Dilation for Incident Cardiovascular Events in a Population-Based Study: The Multi-Ethnic Study of Atherosclerosis , 2009, Circulation.

[7]  K. Kidd,et al.  Refined Geographic Distribution of the Oriental ALDH2*504Lys (nee 487Lys) Variant , 2009, Annals of human genetics.

[8]  M. Marmot,et al.  Endothelial Function Predicts Progression of Carotid Intima-Media Thickness , 2009, Circulation.

[9]  K. Node,et al.  Flow-Mediated Vasodilation as a Diagnostic Modality for Vascular Failure , 2008, Hypertension Research.

[10]  F. Hsu,et al.  Brachial Flow-Mediated Dilation Predicts Incident Cardiovascular Events in Older Adults: The Cardiovascular Health Study , 2007, Circulation.

[11]  K. Kotani,et al.  Status of endothelial dependent vasodilation in patients with hyperuricemia. , 2005, The American journal of cardiology.

[12]  J. Viikari,et al.  Interrelations Between Brachial Endothelial Function and Carotid Intima-Media Thickness in Young Adults: The Cardiovascular Risk in Young Finns Study , 2004, Circulation.

[13]  T. Lehtimäki,et al.  Determinants of Arterial Nitrate-Mediated Dilatation in Children: Role of Oxidized Low-Density Lipoprotein, Endothelial Function, and Carotid Intima-Media Thickness , 2004, Circulation.

[14]  E. Benjamin,et al.  Clinical Correlates and Heritability of Flow-Mediated Dilation in the Community: The Framingham Heart Study , 2004, Circulation.

[15]  F. Hofmann,et al.  Physiology and Pathophysiology of Vascular Signaling Controlled by Cyclic Guanosine 3′,5′-Cyclic Monophosphate–Dependent Protein Kinase , 2003 .

[16]  F. Netter,et al.  Supplemental References , 2002, We Came Naked and Barefoot.

[17]  D. Harrison,et al.  Detection of Superoxide in Vascular Tissue , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[18]  J. Keaney,et al.  Acute effects of vasoactive drug treatment on brachial artery reactivity. , 2002, Journal of the American College of Cardiology.

[19]  T. Singh,et al.  Vascular function and carotid intimal-medial thickness in children with insulin-dependent diabetes mellitus. , 2002, Journal of the American College of Cardiology.

[20]  E. Benjamin,et al.  Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. , 2002, Journal of the American College of Cardiology.

[21]  S. Yoshifuku,et al.  Repeated thermal therapy improves impaired vascular endothelial function in patients with coronary risk factors. , 2001, Journal of the American College of Cardiology.

[22]  O. Raitakari,et al.  Impaired vascular responses to nitroglycerin in subjects with coronary atherosclerosis. , 2001, The American journal of cardiology.

[23]  A M Zeiher,et al.  Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. , 2000, Circulation.

[24]  K. Williams,et al.  Atherosclerosis--an inflammatory disease. , 1999, The New England journal of medicine.

[25]  J. Deanfield,et al.  Smooth muscle dysfunction occurs independently of impaired endothelium-dependent dilation in adults at risk of atherosclerosis. , 1998, Journal of the American College of Cardiology.

[26]  W E Haefeli,et al.  Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. , 1995, Circulation.

[27]  D. Celermajer,et al.  Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. , 1994, Journal of the American College of Cardiology.

[28]  R. Ross.  The pathogenesis of atherosclerosis: a perspective for the 1990s , 1993, Nature.

[29]  J. K. Lloyd,et al.  Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis , 1992, The Lancet.

[30]  P. Wilson,et al.  Coronary risk prediction in adults (the Framingham Heart Study) , 1987, The American journal of cardiology.

[31]  U. Walter,et al.  Physiology and pathophysiology of vascular signaling controlled by guanosine 3',5'-cyclic monophosphate-dependent protein kinase. , 2004, Acta biochimica Polonica.

[32]  F. Hofmann,et al.  Physiology and pathophysiology of vascular signaling controlled by guanosine 3',5'-cyclic monophosphate-dependent protein kinase [corrected]. , 2003, Circulation.

[33]  J. Mckenney,et al.  Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). , 2001, JAMA.

[34]  American Diabetes Association: clinical practice recommendations 1999. , 1999, Diabetes care.

[35]  R Busse,et al.  Crucial role of endothelium in the vasodilator response to increased flow in vivo. , 1986, Hypertension.