|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 2000; 35:71-75 © 2000 by the American College of Cardiology Foundation |
a Department of Internal Medicine III, and the Cardiovascular Research Institute, Kurume University School of Medicine, Kurume, Japan
Manuscript received March 19, 1999; revised manuscript received August 3, 1999, accepted October 5, 1999.
Reprint requests and correspondence: Dr. Hidehiro Matsuoka, Department of Internal Medicine III, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan
matsuoka{at}med.kurume-u.ac.jp
OBJECTIVES
We sought to test whether tetrahydrobiopterin (BH4) supplementation improves nitric oxide (NO) bioactivity in smokers.
BACKGROUND
In smokers, endothelium-derived NO bioactivity is impaired. BH4 is an essential cofactor of NO synthase, and its deficiency decreases NO bioactivity.
METHODS
Sapropterin hydrochloride, an active analogue of BH4 (2 mg/kg body weight), was administered orally to healthy male smokers and age-matched nonsmokers. Before and 3 and 24 h after sapropterin, we measured plasma levels of BH4 and examined flow-mediated vasodilation (FMV) of the brachial artery by high resolution ultrasonography, a noninvasive test of endothelial function.
RESULTS
Basal plasma levels of BH4 were not different between smokers and nonsmokers. Sapropterin administration increased plasma levels of BH4 by threefold at 3 h, which returned to the baseline at 24 h. Before sapropterin, FMV was significantly smaller in smokers (p = 0.0002). Sapropterin significantly augmented endothelium-dependent vasodilation in smokers, but did not affect it in nonsmokers (p = 0.001 by analysis of variance [ANOVA]). Coadministration of NG-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor (20 µmol), into the brachial artery completely abolished the vasodilatory effects of sapropterin (p = 0.002 by ANOVA). Endothelium-independent vasodilation by glyceryl trinitrate was not different between smokers and nonsmokers and was not altered by BH4.
CONCLUSIONS
We demonstrated that BH4 supplementation improved bioactivity of endothelium-derived NO in smokers. These observations strongly suggest that decreased NO-dependent vasodilation in smokers could be related to reduced bioactivity of BH4.
| ||||||||||||||||||||||
This article has been cited by other articles:
|
|
 |
|
  F Cosentino, D Hurlimann, C Delli Gatti, R Chenevard, N Blau, N J Alp, K M Channon, M Eto, P Lerch, F Enseleit, et al. Chronic treatment with tetrahydrobiopterin reverses endothelial dysfunction and oxidative stress in hypercholesterolaemia Heart, April 1, 2008; 94(4): 487 - 492. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Xiao, X. Huang, J. Lawrence, S. Yang, and L. Zhang Fetal and Neonatal Nicotine Exposure Differentially Regulates Vascular Contractility in Adult Male and Female Offspring J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 654 - 661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Moens and D. A. Kass Tetrahydrobiopterin and Cardiovascular Disease Arterioscler. Thromb. Vasc. Biol., November 1, 2006; 26(11): 2439 - 2444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Guo, M. J. Oldham, M. T. Kleinman, R. F. Phalen, and G. S. Kassab Effect of cigarette smoking on nitric oxide, structural, and mechanical properties of mouse arteries Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2354 - H2361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Eskurza, L. A Myerburgh, Z. D Kahn, and D. R Seals Tetrahydrobiopterin augments endothelium-dependent dilatation in sedentary but not in habitually exercising older adults J. Physiol., November 1, 2005; 568(3): 1057 - 1065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sugano, H. Matsuoka, N. Haramaki, H. Umei, E. Murase, K. Fukami, S. Iida, H. Ikeda, and T. Imaizumi Polymorphonuclear Leukocytes May Impair Endothelial Function: Results of Crossover Randomized Study of Lipid-Lowering Therapies Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1262 - 1267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Bots, J. Westerink, T. J. Rabelink, and E. J.P. de Koning Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response Eur. Heart J., February 2, 2005; 26(4): 363 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mochizuki, P. Sipkema, M. Goto, O. Hiramatsu, H. Nakamoto, E. Toyota, T. Kajita, F. Shigeto, T. Yada, Y. Ogasawara, et al. Exogenous NO suppresses flow-induced endothelium-derived NO production because of depletion of tetrahydrobiopterin Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H553 - H558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Blackwell, J. P. Sorenson, D. M. Richardson, L. A. Smith, O. Suda, K. Nath, and Z. S. Katusic Mechanisms of aging-induced impairment of endothelium-dependent relaxation: role of tetrahydrobiopterin Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2448 - H2453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nystrom, A. Nygren, and A. Sjoholm Tetrahydrobiopterin increases insulin sensitivity in patients with type 2 diabetes and coronary heart disease Am J Physiol Endocrinol Metab, November 1, 2004; 287(5): E919 - E925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Kolinsky and S. S. Gross The Mechanism of Potent GTP Cyclohydrolase I Inhibition by 2,4-Diamino-6-hydroxypyrimidine: REQUIREMENT OF THE GTP CYCLOHYDROLASE I FEEDBACK REGULATORY PROTEIN J. Biol. Chem., September 24, 2004; 279(39): 40677 - 40682. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Powers, R. E. Gandley, D. L. Lykins, and J. M. Roberts Moderate Hyperhomocysteinemia Decreases Endothelial-Dependent Vasorelaxation in Pregnant But Not Nonpregnant Mice Hypertension, September 1, 2004; 44(3): 327 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Beckman, J. K. Liao, S. Hurley, L. A. Garrett, D. Chui, D. Mitra, and M. A. Creager Atorvastatin Restores Endothelial Function in Normocholesterolemic Smokers Independent of Changes in Low-Density Lipoprotein Circ. Res., July 23, 2004; 95(2): 217 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. d. C. P. Franco, Z. B. Fortes, E. H. Akamine, E. M. Kawamoto, C. Scavone, L. R. G. de Britto, M. N. Muscara, S. A. Teixeira, R. C. A. Tostes, M. H. C. Carvalho, et al. Tetrahydrobiopterin improves endothelial dysfunction and vascular oxidative stress in microvessels of intrauterine undernourished rats J. Physiol., July 1, 2004; 558(1): 239 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Werner, A. C.F. Gorren, R. Heller, G. Werner-Felmayer, and B. Mayer Tetrahydrobiopterin and Nitric Oxide: Mechanistic and Pharmacological Aspects Experimental Biology and Medicine, December 1, 2003; 228(11): 1291 - 1302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Mitchell, A. M. Dorrance, and R. C. Webb GTP cyclohydrolase 1 inhibition attenuates vasodilation and increases blood pressure in rats Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2165 - H2170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ihlemann, C. Rask-Madsen, A. Perner, H. Dominguez, T. Hermann, L. Kober, and C. Torp-Pedersen Tetrahydrobiopterin restores endothelial dysfunction induced by an oral glucose challenge in healthy subjects Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H875 - H882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Barua, J. A. Ambrose, S. Srivastava, M. C. DeVoe, and L.-J. Eales-Reynolds Reactive Oxygen Species Are Involved in Smoking-Induced Dysfunction of Nitric Oxide Biosynthesis and Upregulation of Endothelial Nitric Oxide Synthase: An In Vitro Demonstration in Human Coronary Artery Endothelial Cells Circulation, May 13, 2003; 107(18): 2342 - 2347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z S Nedeljkovic, N Gokce, and J Loscalzo Mechanisms of oxidative stress and vascular dysfunction Postgrad. Med. J., April 1, 2003; 79(930): 195 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Reaven and P. S. Tsao Insulin resistance and compensatory hyperinsulinemia: The key player between cigarette smoking and cardiovascular disease? J. Am. Coll. Cardiol., March 19, 2003; 41(6): 1044 - 1047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Mitchell, A. M. Dorrance, and R. C. Webb GTP Cyclohydrolase 1 Downregulation Contributes to Glucocorticoid Hypertension in Rats Hypertension, March 1, 2003; 41(3): 669 - 674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Mitchell and R. C. Webb Impaired Vasodilation and Nitric Oxide Synthase Activity in Glucocorticoid-Induced Hypertension Biol Res Nurs, July 1, 2002; 4(1): 16 - 21. [Abstract] [PDF]
|
|
|
|
|
|
M. E. Hyndman, S. Verma, R. J. Rosenfeld, T. J. Anderson, and H. G. Parsons Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial function Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2167 - H2172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Toth, Z. Kukor, and S. Valent Chemical stabilization of tetrahydrobiopterin by L-ascorbic acid: contribution to placental endothelial nitric oxide synthase activity Mol. Hum. Reprod., March 1, 2002; 8(3): 271 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y Fukuda, H Teragawa, K Matsuda, T Yamagata, H Matsuura, and K Chayama Tetrahydrobiopterin restores endothelial function of coronary arteries in patients with hypercholesterolaemia Heart, March 1, 2002; 87(3): 264 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Neunteufl, S. Heher, K. Kostner, G. Mitulovic, S. Lehr, G. Khoschsorur, R. W. Schmid, G. Maurer, and T. Stefenelli Contribution of nicotine to acute endothelial dysfunction in long-term smokers J. Am. Coll. Cardiol., January 16, 2002; 39(2): 251 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. N. Chan, H. M. Colhoun, and P. Vallance Cardiovascular risk factors as determinants of endothelium-dependent and endothelium-independent vascular reactivity in the general population J. Am. Coll. Cardiol., December 1, 2001; 38(7): 1814 - 1820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Shinozaki, A. Hirayama, Y. Nishio, Y. Yoshida, T. Ohtani, T. Okamura, M. Masada, R. Kikkawa, K. Kodama, and A. Kashiwagi Coronary endothelial dysfunction in the insulin-resistant state is linked to abnormal pteridine metabolism and vascular oxidative stress J. Am. Coll. Cardiol., December 1, 2001; 38(7): 1821 - 1828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kanaya, H. Ikeda, N. Haramaki, T. Murohara, and T. Imaizumi Intraplatelet Tetrahydrobiopterin Plays an Important Role in Regulating Canine Coronary Arterial Thrombosis by Modulating Intraplatelet Nitric Oxide and Superoxide Generation Circulation, November 13, 2001; 104(20): 2478 - 2484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Gori, S. S. Mak, S. Kelly, and J. D. Parker Evidence supporting abnormalities in nitric oxide synthase function induced by nitroglycerin in humans J. Am. Coll. Cardiol., October 1, 2001; 38(4): 1096 - 1101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Gori, J. M. Burstein, S. Ahmed, S. E.S. Miner, A. Al-Hesayen, S. Kelly, and J. D. Parker Folic Acid Prevents Nitroglycerin-Induced Nitric Oxide Synthase Dysfunction and Nitrate Tolerance: A Human In Vivo Study Circulation, September 4, 2001; 104(10): 1119 - 1123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. S. Katusic Vascular endothelial dysfunction: does tetrahydrobiopterin play a role? Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H981 - H986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Setoguchi, M. Mohri, H. Shimokawa, and A. Takeshita Tetrahydrobiopterin improves endothelial dysfunction in coronary microcirculation in patients without epicardial coronary artery disease J. Am. Coll. Cardiol., August 1, 2001; 38(2): 493 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Shinozaki, Y. Nishio, T. Okamura, Y. Yoshida, H. Maegawa, H. Kojima, M. Masada, N. Toda, R. Kikkawa, and A. Kashiwagi Oral Administration of Tetrahydrobiopterin Prevents Endothelial Dysfunction and Vascular Oxidative Stress in the Aortas of Insulin-Resistant Rats Circ. Res., September 29, 2000; 87(7): 566 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Heller, A. Unbehaun, B. Schellenberg, B. Mayer, G. Werner-Felmayer, and E. R. Werner L-Ascorbic Acid Potentiates Endothelial Nitric Oxide Synthesis via a Chemical Stabilization of Tetrahydrobiopterin J. Biol. Chem., January 5, 2001; 276(1): 40 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Hyndman, S. Verma, R. J. Rosenfeld, T. J. Anderson, and H. G. Parsons Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial function Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2167 - H2172. [Abstract] [Full Text] [PDF]
|
|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
