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L-Arginine Ameliorates the Abnormal Sympathetic Response of the Dysfunctional Human Coronary Microvasculature

Department of Internal Medicine, Division of Cardiology, The Johns Hopkins Medical Institutions, Baltimore, and the Department of Epidemiology and Preventive Medicine, The University of Maryland, Baltimore, MD.

Joshua M. Hare, MD

Department of Internal Medicine, Division of Cardiology, The Johns Hopkins Medical Institutions, Baltimore, and the Department of Epidemiology and Preventive Medicine, The University of Maryland, Baltimore, MD.

Charles J. Lowenstein, MD

Department of Internal Medicine, Division of Cardiology, The Johns Hopkins Medical Institutions, Baltimore, and the Department of Epidemiology and Preventive Medicine, The University of Maryland, Baltimore, MD.

Gary Gerstenblith, MD

Department of Internal Medicine, Division of Cardiology, The Johns Hopkins Medical Institutions, Baltimore, and the Department of Epidemiology and Preventive Medicine, The University of Maryland, Baltimore, MD.

Vicki Coombs, RN, MS, CCRN

Department of Internal Medicine, Division of Cardiology, The Johns Hopkins Medical Institutions, Baltimore, and the Department of Epidemiology and Preventive Medicine, The University of Maryland, Baltimore, MD.

Patricia Langenberg, PhD

Department of Epidemiology and Preventive Medicine, The University of Maryland, Baltimore, MD.

Jeffrey A. Brinker, MD

Department of Internal Medicine, Division of Cardiology, The Johns Hopkins Medical Institutions, Baltimore, and the Department of Epidemiology and Preventive Medicine, The University of Maryland, Baltimore, MD.

Jon R. Resar, MD

Department of Internal Medicine, Division of Cardiology, The Johns Hopkins Medical Institutions, Baltimore, and the Department of Epidemiology and Preventive Medicine, The University of Maryland, Baltimore, MD.

A nitric oxide (NO)-related defect may contribute to abnormal coronary sympathetic responses that can cause ischemia in patients with endothelial dysfunction. Because L-arginine, the NO synthase (NOS) precursor, augments NO bioactivity, we hypothesized that L-arginine would improve dysfunctional coronary sympathetic responses. Eleven patients with atherosclerosis or its risk factors were challenged with the cold pressor test, a specific provocative test of cardiac sympathetic activity, after 3 separate and sequential intracoronary infusions, as follows: 1) Normal saline; 2) L-NMMA, a competitive inhibitor of NOS; and 3) L-arginine. Study patients exhibited abnormal microvascular responses with coronary vascular resistance (CVR) increasing by 22.3 ±9.7% (mean ± 1 SEM), p<0.01. In addition, the change in coronary blood flow (CBF) did not correlate with the change in rate pressure product (RPP), r = -0.29, p = NS, suggesting an uncoupling of CBF from cardiac work. In the presence of L-NMMA, the CVR response, 10.3 ±9.8%, did not differ from the baseline response, and there was no relationship between the changes in CBF and RPP, r=0.13, p = NS. In contrast, L-arginine ameliorated the CVR response, -3.2 ±3.1%, p<0.05 vs baseline response, and restored the normal correlation between the changes in CBF and RPP, r = 0.74, p<0.01. L-arginine not only improved abnormal microvascular responses to sympathetic activation, but it also restored the coupling that normally exists between coronary blood flow and cardiac work. L-arginine warrants further investigation as a therapy for coronary artery disease.

Angiology, Vol. 55, No. 1, 1-8 (2004)
DOI: 10.1177/000331970405500101


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