Endothelial dysfunction in hypercholesterolemia is reversed by a nutritional product designed to enhance nitric oxide activity

被引:41
作者
Maxwell, AJ
Anderson, B
Zapien, MP
Cooke, JP
机构
[1] Cooke Pharma Inc, Belmont, MA USA
[2] Stanford Univ, Div Cardiovasc Med, Palo Alto, CA 94304 USA
关键词
L-arginine; hypercholesterolemia; atherosclerosis; blood flow; nitric oxide; vasoconstriction; dilation; endothelial function;
D O I
10.1023/A:1007886725480
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The objective of this study was to investigate the vascular and biochemical effects of a formulated product in the form of a bar enriched with a combination of nutrients known to enhance the synthesis or activity of endothelium-derived nitric oxide (EDNO). Individuals with hypercholesterolemia manifest impaired flow-mediated vasodilation, which is largely due to a reduction in EDNO activity. Oral supplementation with large amounts (6-21 g/day) of L-arginine, the precursor of EDNO, have been shown to improve endothelium-mediated vasodilation in hypercholesterolemia. Such large doses are effective but may be impractical to take in capsule form. Accordingly, we have developed a nutrient bar enriched with L-arginine as well as other ingredients that additively enhance EDNO activity. A pilot study in 41 hypercholesterolemic individuals indicated that the bar was well tolerated, had no adverse effects on serum chemistries or lipid profile, and normalized endothelial vasodilator function. To definitively determine if the nutrient bar normalizes endothelial function, a double-blind, placebo-controlled study was performed. Flow-mediated endothelium-dependent vasodilation was assessed by high-resolution ultrasonography before and after 1 week of bar use (2 bars/day) in an additional group of 43 volunteer subjects (57 +/- 10 years old; 22 men, 21 women) with hypercholesterolemia. Subjects manifested an impaired flow-mediated vasodilation before the intervention. Vasodilator function in the active bar group improved to within a normal range (6.5 +/- 3% before to 10 +/- 5% after, P = 0.02; normal, 12 +/- 3%) and was significantly better (P < 0.01) than in the placebo bar group (7.1 +/- 3% before to 6.7 +/- 4% after). These findings reveal that use of a nutrient bar designed to enhance EDNO activity improves flow-mediated endothelium-dependent vasodilation in hypercholesterolemic individuals.
引用
收藏
页码:309 / 316
页数:8
相关论文
共 49 条
  • [11] Regression or progression - Dependency on vascular nitric oxide
    Candipan, RC
    Wang, BY
    Buitrago, R
    Tsao, PS
    Cooke, JP
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1996, 16 (01) : 44 - 50
  • [12] NONINVASIVE DETECTION OF ENDOTHELIAL DYSFUNCTION IN CHILDREN AND ADULTS AT RISK OF ATHEROSCLEROSIS
    CELERMAJER, DS
    SORENSEN, KE
    GOOCH, VM
    SPIEGELHALTER, DJ
    MILLER, OI
    SULLIVAN, ID
    LLOYD, JK
    DEANFIELD, JE
    [J]. LANCET, 1992, 340 (8828) : 1111 - 1115
  • [13] Endothelial dysfunction: Does it matter? Is it reversible?
    Celermajer, DS
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1997, 30 (02) : 325 - 333
  • [14] Effect of supplemental oral L-arginine on exercise capacity in patients with stable angina pectoris
    Ceremuzynski, L
    Chamiec, T
    HerbaczynskaCedro, K
    [J]. AMERICAN JOURNAL OF CARDIOLOGY, 1997, 80 (03) : 331 - &
  • [15] Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults
    Clarkson, P
    Adams, MR
    Powe, AJ
    Donald, AE
    McCredie, R
    Robinson, J
    McCarthy, SN
    Keech, A
    Celermajer, DS
    Deanfield, JE
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1996, 97 (08) : 1989 - 1994
  • [16] ANTIATHEROGENIC EFFECTS OF L-ARGININE IN THE HYPERCHOLESTEROLEMIC RABBIT
    COOKE, JP
    SINGER, AH
    TSAO, P
    ZERA, P
    ROWAN, RA
    BILLINGHAM, ME
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (03) : 1168 - 1172
  • [17] COOKE JP, 1997, ENDOTHELIAL FUNCTION, P29
  • [18] L-ARGININE IMPROVES ENDOTHELIUM-DEPENDENT VASODILATION IN HYPERCHOLESTEROLEMIC HUMANS
    CREAGER, MA
    GALLAGHER, SJ
    GIRERD, XJ
    COLEMAN, SM
    DZAU, VJ
    COOKE, JP
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (04) : 1248 - 1253
  • [19] L-arginine supplementation improves venous endothelial cell but not smooth muscle cell dysfunction induced by prolonged diet-induced hypercholesterolemia
    Davies, MG
    Barber, E
    Dalen, H
    Hagen, PO
    [J]. JOURNAL OF INVESTIGATIVE SURGERY, 1996, 9 (06) : 415 - 422
  • [20] EFFECT OF L-ARGININE ON CORONARY ENDOTHELIAL FUNCTION IN CARDIAC TRANSPLANT RECIPIENTS - RELATION TO VESSEL WALL MORPHOLOGY
    DREXLER, H
    FISCHELL, TA
    PINTO, FJ
    CHENZBRAUN, A
    BOTAS, J
    COOKE, JP
    ALDERMAN, EL
    [J]. CIRCULATION, 1994, 89 (04) : 1615 - 1623