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CLINICAL RESEARCH: ATHEROSCLEROSIS RISK

Low body mass index is a risk factor forimpaired endothelium-dependent vasodilation in humans: role of nitric oxide and oxidative stress

Yukihito Higashi, MD, PhD^*,*, Shota Sasaki, MD, Keigo Nakagawa, MD, Masashi Kimura, MD, Kensuke Noma, MD, Satoshi Sasaki, MD, Keiko Hara, MD, Hideo Matsuura, MD, PhD, Chikara Goto, RPT, MS, Tetsuya Oshima, MD, PhD, Kazuaki Chayama, MD, PhD and Masao Yoshizumi, MD, PhD^*

^* Department of Cardiovascular Physiology and Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan
Department of Medicine and Molecular Science, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan
Division of Physical Therapy, Institute of Health Sciences, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan
Department of Clinical Laboratory Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan

Manuscript received May 20, 2002; revised manuscript received January 27, 2003, accepted March 7, 2003.

^* Reprint requests and correspondence: Dr. Yukihito Higashi, Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
yhigashi{at}hiroshima-u.ac.jp

OBJECTIVES: The purpose of this study was to evaluate the relationship between body mass index (BMI), including low BMIs, and endothelial function.

BACKGROUND: Epidemiologic study has demonstrated that not only obesity but also a low BMI may be a risk factor for cardiovascular disease.

METHODS: The forearm blood flow (FBF) response to acetylcholine (ACh) and isosorbide dinitrate (ISDN) was measured in 87 healthy young men (15 low BMI, 51 normal, 14 obese, and 7 extremely obese).

RESULTS: Plasma concentrations of 8-hydroxy-2'-deoxyguanosine and serum concentrations of malondialdehyde-modified low-density lipoprotein were higher in low BMI, obese, and extremely obese subjects than in normal subjects and were similar among the low BMI, obese, and extremely obese groups. The FBF response to ACh was greater in the normal group than in the other groups (p < 0.001), and was lower in the extremely obese group as compared with the other groups (p < 0.001). The ACh-stimulated vasodilation was similar between the low BMI group and the obese group. The ISDN-stimulated vasodilation was similar in all four groups. There were no significant differences in ACh-stimulated vasodilation between the four groups after the nitric oxide (NO) synthase inhibitor N^G-monomethyl-L-arginine infusion. Co-infusion of vitamin C augmented the FBF response to ACh in low BMI, obese, and extremely obese groups—but not in normal BMI group.

CONCLUSIONS: These findings suggest that not only obesity but also a low BMI may be a risk factor for impaired endothelium-dependent vasodilation through the increased oxidative stress, leading to the reduced bioavailability of NO.

Abbreviations and Acronyms   ACh   acetylcholine   BMI   body mass index   BP   blood pressure   DNA   deoxyribonucleic acid   FBF   forearm blood flow   HOMA   homeostatic model assessment   ISDN   isosorbide dinitrate   L-NMMA   NG-monomethyl-L-arginine   MDA-LDL   malondialdehyde-modified low-density lipoprotein   NO   nitric oxide   NOx   nitrate/nitrite   8-OHdG   8-hydroxy-2'-deoxyguanosine

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