Tetrahydrobiopterin enhances forearm vascular response to acetylcholine in both normotensive and hypertensive individuals
Abstract
BACKGROUND: A deficiency of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide (NO) synthase, decreases NO synthesis and increases superoxide production. Supplementation of BH4 has been postulated to improve endothelial function in atherosclerotic patients. The purpose of this study was to determine whether BH4 restores endothelium-dependent vasodilation in patients with essential hypertension. METHODS: We evaluated the effects of BH4 on forearm vascular responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, both in patients with essential hypertension and in age- and sex-matched normal control subjects. Forearm blood flow (FBF) was measured using strain gauge plethysmography. RESULTS: The response of FBF to ACh was less in hypertensive patients (n = 8) than in normal control subjects (n = 8). There was no significant difference in FBF response to ISDN in the two groups. During coinfusion of BH4 (500 mg/min), the FBF response to ACh in hypertensive patients increased significantly (14.8 +/- 4.6 to 25.6 +/- 7.3 mL/min/100 mL tissue, P < .05) to the level of normal control subjects. In the control subjects, also, BH4 augmented the FBF response to ACh (27.8 +/- 8.7 to 36.1 +/- 9.6 mL/min/100 mL tissue, P < .05). The increase in FBF after ISDN was not altered by BH4 in either group (each group, n = 6). CONCLUSION: Supplementation of BH4 augments endothelium-dependent vasodilation in both normotensive and hypertensive individuals.
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Low levels of BH4 are found in endothelial dysfunction and cardiovascular disease.
“Conversely, low levels of BH4 are found in endothelial dysfunction and cardiovascular disease (421, 429, 440, 550, 560, 858, 899).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [429]
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Cites
Friedewald, W. T., Levy, R. I., & Fredrickson, D. S. (1972) · Clinical Chemistry · doi:10.1093/clinchem/18.6.499 · Cited by 32,423 · see citing works
Abnormal Endothelium-Dependent Vascular Relaxation in Patients with Essential Hypertension
Panza, J. A., Quyyumi, A. A., Brush, J. E., & Epstein, S. E. (1990) · New England Journal of Medicine · doi:10.1056/nejm199007053230105 · Cited by 2,366 · see citing works
Endothelium‐derived relaxing and contracting factors
Furchgott, R. F., & Vanhoutte, P. M. (1989) · The FASEB Journal · doi:10.1096/fasebj.3.9.2545495 · Cited by 2,007 · see citing works
Role of endothelium-derived nitric oxide in the regulation of blood pressure.
Rees, D. D., Palmer, R. M. J., & Moncada, S. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.9.3375 · Cited by 1,827 · see citing works
Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man
Vallance, P., Collier, J., & Moncada, S. (1989) · The Lancet · doi:10.1016/s0140-6736(89)91013-1 · Cited by 1,590 · see citing works
Linder, L., Kiowski, W., Bühler, F. R., & Lüscher, T. F. (1990) · Circulation · doi:10.1161/01.cir.81.6.1762 · Cited by 797 · see citing works
CARTER, V. B. (1951) · PubMed · Cited by 741 · see citing works
Aging and Endothelial Function in Normotensive Subjects and Patients With Essential Hypertension
Taddei, S., Virdis, A., Mattei, P., Ghiadoni, L., Gennari, A., Fasolo, C. B., Sudano, I., & Salvetti, A. (1995) · Circulation · doi:10.1161/01.cir.91.7.1981 · Cited by 710 · see citing works
Tetrahydrobiopterin restores endothelial function in hypercholesterolemia.
Stroes, E. S. G., Kastelein, J. J. P., Cosentino, F., Erkelens, W. D., Wever, R. M. F., Koomans, H. A., Lüscher, T. F., & Rabelink, T. J. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119131 · Cited by 588 · see citing works
Higashi, Y., Sasaki, S., Kurisu, S., Yoshimizu, A., Sasaki, N., Matsuura, H., Kajiyama, G., & Oshima, T. (1999) · Circulation · doi:10.1161/01.cir.100.11.1194 · Cited by 552 · see citing works
Self-citationCa2+/calmodulin-dependent formation of hydrogen peroxide by brain nitric oxide synthase
Heinzel, B., John, M., Klatt, P., Böhme, E., & Mayer, B. (1992) · Biochemical Journal · doi:10.1042/bj2810627 · Cited by 530 · see citing works
Treasure, C. B., Klein, J. L., Vita, J. A., Manoukian, S. V., Renwick, G. H., Selwyn, A. P., Ganz, P., & Alexander, R. W. (1993) · Circulation · doi:10.1161/01.cir.87.1.86 · Cited by 392 · see citing works
The role of nitric oxide in endothelium-dependent vasodilation of hypercholesterolemic patients.
Casino, P. R., Kilcoyne, C. M., Quyyumi, A. A., Hoeg, J. M., & Panza, J. A. (1993) · Circulation · doi:10.1161/01.cir.88.6.2541 · Cited by 366 · see citing works
Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats.
Cosentino, F., Patton, S. R., d’Uscio, L. V., Werner, E. R., Werner‐Felmayer, G., Moreau, P. R., Maliñski, T., & Lüscher, T. F. (1998) · Journal of Clinical Investigation · doi:10.1172/jci650 · Cited by 351 · see citing works
Endothelial Nitric-oxide Synthase
Rodríguez‐Crespo, I., Gerber, N. C., & de Montellano, P. R. O. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.19.11462 · Cited by 323 · see citing works
Tetrahydrobiopterin and Dysfunction of Endothelial Nitric Oxide Synthase in Coronary Arteries
Cosentino, F., & Katušić, Z. S. (1995) · Circulation · doi:10.1161/01.cir.91.1.139 · Cited by 294 · see citing works
Werner-Felmayer, G., Werner, E. R., Fuchs, D., Hausen, A., Reibnegger, G., Schmidt, K., Weiss, G., & Wachter, H. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53931-4 · Cited by 263 · see citing works
Imbalance of Endothelium-derived Relaxing and Contracting Factors: A New Concept in Hypertension?
Lüscher, T. F. (1990) · American Journal of Hypertension · doi:10.1093/ajh/3.4.317 · Cited by 246 · see citing works
l -Arginine Induces Nitric Oxide–Dependent Vasodilation in Patients With Critical Limb Ischemia
Bode‐Böger, S. M., Böger, R. H., Alfke, H., Heinzel, D., Tsikas, D., Creutzig, A., Alexander, K., & Frölich, J. C. (1996) · Circulation · doi:10.1161/01.cir.93.1.85 · Cited by 196 · see citing works
Schiffrin, E. L., & Deng, L.-Y. (1995) · Hypertension · doi:10.1161/01.hyp.25.4.699 · Cited by 192 · see citing works
Egashira, K., Suzuki, S. O., Hirooka, Y., Kai, H., Sugimachi, M., Imaizumi, T., & Takeshita, A. (1995) · Hypertension · doi:10.1161/01.hyp.25.2.201 · Cited by 191 · see citing works
Daily Aerobic Exercise Improves Reactive Hyperemia in Patients With Essential Hypertension
Higashi, Y., Sasaki, S., Sasaki, N., Nakagawa, K., Ueda, T., Yoshimizu, A., Kurisu, S., Matsuura, H., Kajiyama, G., & Oshima, T. (1999) · Hypertension · doi:10.1161/01.hyp.33.1.591 · Cited by 181 · see citing works
Self-citationHigashi, Y., Sasaki, S., Nakagawa, K., Ueda, T., Yoshimizu, A., Kurisu, S., Matsuura, H., Kajiyama, G., & Oshima, T. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(99)00561-6 · Cited by 171 · see citing works
Self-citationSmoking Impairs the Activity of Endothelial Nitric Oxide Synthase in Saphenous Vein
Higman, D. J., Strachan, A. M. J., Buttery, L. D. K., Hicks, R., Springall, D. R., Greenhalgh, R. M., & Powell, J. T. (1996) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.16.4.546 · Cited by 155 · see citing works
New Tetrahydrobiopterin-Dependent Systems
Kaufman, S. (1993) · Annual Review of Nutrition · doi:10.1146/annurev.nu.13.070193.001401 · Cited by 147 · see citing works
New Tetrahydrobiopterin-Dependent Systems
Kaufman, S. (1993) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.13.1.261 · Cited by 147 · see citing works
Effects of l -Arginine Infusion on Renal Hemodynamics in Patients With Mild Essential Hypertension
Higashi, Y., Oshima, T., Ozono, R., Watanabe, M., Matsuura, H., & Kajiyama, G. (1995) · Hypertension · doi:10.1161/01.hyp.25.4.898 · Cited by 104 · see citing works
Self-citationHigashi, Y., Oshima, T., Ozono, R., Matsuura, H., & Kajiyama, G. (1997) · Hypertension · doi:10.1161/01.hyp.30.2.252 · Cited by 102 · see citing works
Self-citationHirooka, Y., Egashira, K., Imaizumi, T., Tagawa, T., Kai, H., Sugimachi, M., & Takeshita, A. (1994) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(94)90854-0 · Cited by 96 · see citing works
Higashi, Y., Oshima, T., Sasaki, S., Nakano, Y., Kambe, M., Matsuura, H., & Kajiyama, G. (1998) · Hypertension · doi:10.1161/01.hyp.32.1.16 · Cited by 56 · see citing works
Self-citationTetrahydrobiopterin induces vasodilatation via enhancement of cGMP level
van Amsterdam, J., & Wemer, J. (1992) · European Journal of Pharmacology · doi:10.1016/0014-2999(92)90056-a · Cited by 18 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [18]18. Hinzel B, John M, Klatt P, Bohem E, Mayer B: Ca 2 + /calmodulindependent formation of hydrogen peroxide by brain nitric oxide synthase. Biochem J 1992;281:627630.
- [26]26. Werner-Felmayer G, Werner ER, Fuchs D, Hausen A, Reibnegger G, Schmidt K, Weiss G, Wachter H: Pteridine biosynthesis in human endothelial cells. J Biol Chem 1993;268:18421846.
Cited by
Sorted by citations
Nitric oxide synthases: regulation and function
Forstermann, U., & Sessa, W. C. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehr304 · Cited by 4,409 · see citing works
Endothelial Nitric Oxide Synthase in Vascular Disease: From Marvel to Menace
Förstermann, U., & Münzel, T. (2006) · Circulation · doi:10.1161/circulationaha.105.602532 · Cited by 1,957 · see citing works
Incalza, M. A., D’Oria, R., Natalicchio, A., Perrini, S., Laviola, L., & Giorgino, F. (2017) · Vascular Pharmacology · doi:10.1016/j.vph.2017.05.005 · Cited by 1,375 · see citing works
Role of oxidative stress in atherosclerosis
Harrison, D., Griendling, K. K., Landmesser, U., Hornig, B., & Drexler, H. (2003) · The American Journal of Cardiology · doi:10.1016/s0002-9149(02)03144-2 · Cited by 1,275 · see citing works
Vascular nitric oxide: Beyond eNOS
Zhao, Y., Vanhoutte, P. M., & Leung, S. W. S. (2015) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2015.09.002 · Cited by 823 · see citing works
Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture)
Félétou, M., & Vanhoutte, P. M. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00292.2006 · Cited by 818 · see citing works
Endothelial Function and Oxidative Stress in Cardiovascular Diseases
Higashi, Y., Noma, K., Yoshizumi, M., & Kihara, Y. (2009) · Circulation Journal · doi:10.1253/circj.cj-08-1102 · Cited by 796 · see citing works
Self-citationNitric oxide and oxidative stress in vascular disease
Förstermann, U. (2010) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-010-0808-2 · Cited by 780 · see citing works
Reactive oxygen species in vascular biology: implications in hypertension
Touyz, R. M., & Schiffrin, E. L. (2004) · Histochemistry and Cell Biology · doi:10.1007/s00418-004-0696-7 · Cited by 646 · see citing works
Oxidative Stress and Hypertension
Griendling, K. K., Camargo, L. L., Rios, F. J. O., Alves-Lopes, R., Montezano, A. C. I., & Touyz, R. M. (2021) · Circulation Research · doi:10.1161/circresaha.121.318063 · Cited by 592 · see citing works
Oxidative stress in vascular disease: causes, defense mechanisms and potential therapies
Förstermann, U. (2008) · Nature Clinical Practice Cardiovascular Medicine · doi:10.1038/ncpcardio1211 · Cited by 576 · see citing works
ROS-triggered endothelial cell death mechanisms: Focus on pyroptosis, parthanatos, and ferroptosis
Zheng, D., Liu, J., Piao, H., Zhu, Z., Wei, R., & Liu, K. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1039241 · Cited by 574 · see citing works
Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541 · see citing works
Oxidative stress and endothelial dysfunction in hypertension
Schulz, E., Gori, T., & Münzel, T. F. (2011) · Hypertension Research · doi:10.1038/hr.2011.39 · Cited by 503 · see citing works
Tetrahydrobiopterin: biochemistry and pathophysiology
Werner, E. R., Blau, N., & Thöny, B. (2011) · Biochemical Journal · doi:10.1042/bj20110293 · Cited by 493 · see citing works
Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension
Schulz, E., Jansen, T., Wenzel, P., Daiber, A., & Münzel, T. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1989 · Cited by 430 · see citing works
Thomas, S. R., Witting, P. K., & Drummond, G. R. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2027 · Cited by 383 · see citing works
Janaszak-Jasiecka, A., Płoska, A., Wierońska, J. M., Dobrucki, L. W., & Kalinowski, L. (2023) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-023-00423-2 · Cited by 358 · see citing works
Hermann, M., Flammer, A. J., & Lüscher, T. F. (2006) · Journal of Clinical Hypertension · doi:10.1111/j.1524-6175.2006.06032.x · Cited by 356 · see citing works
Oxidative Stress and Human Hypertension: Vascular Mechanisms, Biomarkers, and Novel Therapies
Montezano, A. C. I., Dulak-Lis, M. G., Tsiropoulou, S., Harvey, A., Briones, A. M., & Touyz, R. M. (2015) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2015.02.008 · Cited by 324 · see citing works
Reactive oxygen species and ischemic cerebrovascular disease
Olmez, I., & Özyurt, H. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2011.11.009 · Cited by 301 · see citing works
Förstermann, U., & Li, H. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01196.x · Cited by 299 · see citing works
Role of oxidative stress and nitric oxide in atherothrombosis
Lubos, E. (2008) · Frontiers in bioscience · doi:10.2741/3084 · Cited by 290 · see citing works
Oxidative stress and the role of redox signalling in chronic kidney disease
Kishi, S., Nagasu, H., Kidokoro, K., & Kashihara, N. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00775-0 · Cited by 283 · see citing works
Higashi, Y., & Yoshizumi, M. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.02.003 · Cited by 262 · see citing works
Self-citationEndothelial dysfunction and hypertension in aging
Higashi, Y., Kihara, Y., & Noma, K. (2012) · Hypertension Research · doi:10.1038/hr.2012.138 · Cited by 265 · see citing works
Self-citationResveratrol blunts the positive effects of exercise training on cardiovascular health in aged men
Gliemann, L., Schmidt, J. F., Olesen, J., Biensø, R. S., Peronard, S. L., Grandjean, S. U., Mortensen, S. P., Nyberg, M., Bangsbo, J., Pilegaard, H., et al. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.258061 · Cited by 244 · see citing works
Redox Signaling, Vascular Function, and Hypertension
Lee, M. Y., & Griendling, K. K. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1986 · Cited by 241 · see citing works
Mechanisms and consequences of endothelial nitric oxide synthase dysfunction in hypertension
Li, Q., Youn, J.-Y., & Cai, H. “. (2015) · Journal of Hypertension · doi:10.1097/hjh.0000000000000587 · Cited by 237 · see citing works
Tetrahydrobiopterin in Cardiovascular Health and Disease
Bendall, J. K., Douglas, G., McNeill, E., Channon, K. M., & Crabtree, M. J. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5566 · Cited by 231 · see citing works
Synthesis and recycling of tetrahydrobiopterin in endothelial function and vascular disease
Crabtree, M. J., & Channon, K. M. (2011) · Nitric Oxide · doi:10.1016/j.niox.2011.04.004 · Cited by 223 · see citing works
Kietadisorn, R., Juni, R. P., & Moens, A. L. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00540.2011 · Cited by 216 · see citing works
Oxidative stress and endothelial dysfunction: Clinical evidence and therapeutic implications
Higashi, Y., Maruhashi, T., Noma, K., & Kihara, Y. (2013) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2013.12.001 · Cited by 216 · see citing works
Self-citationHydrogen peroxide signaling in vascular endothelial cells
Bretón-Romero, R., & Lamas, S. (2014) · Redox Biology · doi:10.1016/j.redox.2014.02.005 · Cited by 209 · see citing works
Crabtree, M. J., Smith, C. L., Lam, G., Goligorsky, M. S., & Gross, S. S. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00823.2007 · Cited by 213 · see citing works
Altaany, Z., Ju, Y., Yang, G., & Wang, R. (2014) · Science Signaling · doi:10.1126/scisignal.2005478 · Cited by 209 · see citing works
The Role of Nitroglycerin and Other Nitrogen Oxides in Cardiovascular Therapeutics
Divakaran, S., & Loscalzo, J. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.09.1064 · Cited by 209 · see citing works
Endothelial dysfunction: a strategic target in the treatment of hypertension?
Tang, E. H. C., & Vanhoutte, P. M. (2010) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-010-0786-4 · Cited by 182 · see citing works
Platelet-Derived Nitric Oxide Signaling and Regulation
Gkaliagkousi, Ε., Ritter, J. M., & Ferro, A. (2007) · Circulation Research · doi:10.1161/circresaha.107.158410 · Cited by 175 · see citing works
Post-translational regulation of endothelial nitric oxide synthase in vascular endothelium
Qian, J., & Fulton, D. J. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00347 · Cited by 176 · see citing works
The eNOS signalosome and its link to endothelial dysfunction
Siragusa, M., & Fleming, I. (2016) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-016-1839-0 · Cited by 171 · see citing works
Oxidative Stress and Vascular Function: Implications for Pharmacologic Treatments
Weseler, A. R., & Bast, A. (2010) · Current Hypertension Reports · doi:10.1007/s11906-010-0103-9 · Cited by 161 · see citing works
Frombaum, M., Clanche, S. L., Bonnefont‐Rousselot, D., & Borderie, D. (2011) · Biochimie · doi:10.1016/j.biochi.2011.11.001 · Cited by 156 · see citing works
Förstermann, U. (2006) · Biological Chemistry · doi:10.1515/bc.2006.190 · Cited by 153 · see citing works
Prevention of Atherosclerosis by Interference with the Vascular Nitric Oxide System
Li, H., & Förstermann, U. (2009) · Current Pharmaceutical Design · doi:10.2174/138161209789058002 · Cited by 149 · see citing works
Metabolic reprogramming, oxidative stress, and pulmonary hypertension
Pokharel, M. D., Marciano, D. P., Fu, P., Franco, M. C., Unwalla, H. J., Tieu, K., Fineman, J. R., Wang, T., & Black, S. M. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102797 · Cited by 151 · see citing works
Reactive oxygen species in hypertension
Camargo, L. L., Rios, F. J. O., Montezano, A. C. I., & Touyz, R. M. (2024) · Nature Reviews Cardiology · doi:10.1038/s41569-024-01062-6 · Cited by 154 · see citing works
Tetrahydrobiopterin and Nitric Oxide: Mechanistic and Pharmacological Aspects
Werner, E. R., Gorren, A. C. F., Heller, R., Werner‐Felmayer, G., & Mayer, B. (2003) · Experimental Biology and Medicine · doi:10.1177/153537020322801108 · Cited by 144 · see citing works
Vascular protection by tetrahydrobiopterin: progress and therapeutic prospects
Katušić, Z. S., d’Uscio, L. V., & Nath, K. A. (2008) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2008.10.003 · Cited by 141 · see citing works
Endothelial Function in Dyslipidemia: Roles of LDL-Cholesterol, HDL-Cholesterol and Triglycerides
Higashi, Y. (2023) · Cells · doi:10.3390/cells12091293 · Cited by 140 · see citing works
Self-citationRecoupling the Cardiac Nitric Oxide Synthases: Tetrahydrobiopterin Synthesis and Recycling
Alkaitis, M. S., & Crabtree, M. J. (2012) · Current Heart Failure Reports · doi:10.1007/s11897-012-0097-5 · Cited by 139 · see citing works
Effect of high-salt diet on NO release and superoxide production in rat aorta
Zhu, J., Mori, T., Huang, T., & Lombard, J. H. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00331.2003 · Cited by 121 · see citing works
Masi, S., Uliana, M., & Virdis, A. (2019) · Vascular Pharmacology · doi:10.1016/j.vph.2019.01.004 · Cited by 119 · see citing works
Endothelial dysfunction in conduit arteries and in microcirculation. Novel therapeutic approaches
Tousoulis, D., Simopoulou, C., Παπαγεωργίου, Ν., Oikonomou, E. K., Hatzis, G., Siasos, G., Tsiamis, E. G., & Stefanadis, C. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.06.003 · Cited by 117 · see citing works
Oxidative Stress and Vascular Damage in Hypertension: Role of Angiotensin II
Virdis, A., Duranti, E., & Taddei, S. (2011) · International Journal of Hypertension · doi:10.4061/2011/916310 · Cited by 116 · see citing works
SMITH, A. R. W., Visioli, F., Frei, B. B., & Hagen, T. M. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00232.x · Cited by 116 · see citing works
Hypercapnia Impairs Lung Neutrophil Function and Increases Mortality in Murine Pseudomonas Pneumonia
Gates, K. L., Howell, H. A., Nair, A., Vohwinkel, C. U., Welch, L. C., Beitel, G. J., Hauser, A. R., Sznajder, J. I., & Sporn, P. H. S. (2013) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2012-0487oc · Cited by 115 · see citing works
Wang, S., Xu, J., Song, P., Wu, Y., Zhang, J., Choi, H. C., & Zou, M. (2008) · Hypertension · doi:10.1161/hypertensionaha.108.112094 · Cited by 110 · see citing works
Nyberg, M., Gliemann, L., Thaning, P., Hellsten, Y., & Mortensen, S. P. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2011.225136 · Cited by 108 · see citing works
Hernanz, R., Briones, A. M., Salaíces, M., & Alonso, M. J. (2013) · Clinical Science · doi:10.1042/cs20120651 · Cited by 100 · see citing works
Tetrahydrobiopterin: a novel antihypertensive therapy
Porkert, M., Sher, S., Reddy, U., Cheema, F. H., Niessner, C., Kolm, P., Jones, D. P., Hooper, C. W., Taylor, W. R., Harrison, D. G., et al. (2008) · Journal of Human Hypertension · doi:10.1038/sj.jhh.1002329 · Cited by 99 · see citing works
Moreau, K. L., Meditz, A. L., Deane, K. D., & Kohrt, W. M. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01065.2011 · Cited by 99 · see citing works
Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases
Forte, M., Conti, V., Damato, A., Ambrosio, M., Puca, A. A., Sciarretta, S., Frati, G., Vecchione, C., & Carrizzo, A. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/7364138 · Cited by 96 · see citing works
The Future Challenge of Reactive Oxygen Species (ROS) in Hypertension: From Bench to Bed Side
Togliatto, G., Lombardo, G., & Brizzi, M. F. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18091988 · Cited by 98 · see citing works
Łuczak, A., Madej, M., Kasprzyk, A., & Doroszko, A. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/1417981 · Cited by 90 · see citing works
Higashi, Y., & Yoshizumi, M. (2003) · Journal of Pharmacological Sciences · doi:10.1254/jphs.93.399 · Cited by 85 · see citing works
Self-citationTherapeutic Potential of Tetrahydrobiopterin for Treating Vascular and Cardiac Disease
Moens, A. L., & Kass, D. A. (2007) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e318123f854 · Cited by 83 · see citing works
Hypertension: What's Sex Got to do With It?
Zimmerman, M. A., & Sullivan, J. C. (2013) · Physiology · doi:10.1152/physiol.00013.2013 · Cited by 82 · see citing works
Smoking cessation and vascular endothelial function
Higashi, Y. (2023) · Hypertension Research · doi:10.1038/s41440-023-01455-z · Cited by 84 · see citing works
Self-citationRoy, B. (2025) · Medical Sciences · doi:10.3390/medsci13030087 · Cited by 89 · see citing works
New Insights into the Role of Oxidative Stress in Scleroderma Fibrosis
Gabrielli, A., Svegliati, S., Moroncini, G., & Amico, D. (2012) · The Open Rheumatology Journal · doi:10.2174/1874312901206010087 · Cited by 76 · see citing works
Maiocchi, S. L., Ku, J., Thai, T., Chan, E., Rees, M. D., & Thomas, S. R. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107711 · Cited by 75 · see citing works
The Role of Reactive Oxygen Species in Microvascular Remodeling
Staiculescu, M. C., Foote, C. A., Meininger, G. A., & Martinez‐Lemus, L. A. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151223792 · Cited by 76 · see citing works
Hemmingsen, J. G., Rissler, J., Lykkesfeldt, J., Sällsten, G., Kristiansen, J., Peter Møller, P., & Loft, S. H. (2015) · Particle and Fibre Toxicology · doi:10.1186/s12989-015-0081-9 · Cited by 66 · see citing works
Assessment of Endothelial Function
Higashi, Y. (2015) · International Heart Journal · doi:10.1536/ihj.14-385 · Cited by 66 · see citing works
Self-citationKumar, G., Dey, S. K., & Kundu, S. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118377 · Cited by 68 · see citing works
The role of tetrahydrobiopterin in inflammation and cardiovascular disease
McNeill, E., & Channon, K. M. (2012) · Thrombosis and Haemostasis · doi:10.1160/th12-06-0424 · Cited by 60 · see citing works
Regulation of NOS expression in vascular diseases
Pautz, A., Li, H., & Kleinert, H. (2021) · Frontiers in Bioscience-Landmark · doi:10.52586/4926 · Cited by 63 · see citing works
Promotion of nitric oxide production: mechanisms, strategies, and possibilities
Gonzalez, M., Clayton, S., Wauson, E., Christian, D., & Tran, Q. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1545044 · Cited by 56 · see citing works
Endothelium-derived vasoactive agents, AT1 receptors and inflammation
MacKenzie, A. R. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.11.001 · Cited by 55 · see citing works
Zhang, M., Song, P., Xu, J., & Zou, M. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.207712 · Cited by 55 · see citing works
The antihypertensive effect of arginine
Vasdev, S., & Gill, V. D. (2008) · International Journal of Angiology · doi:10.1055/s-0031-1278274 · Cited by 53 · see citing works
Tetrahydrobiopterin: pleiotropic roles in cardiovascular pathophysiology
Cunnington, C., & Channon, K. M. (2010) · Heart · doi:10.1136/hrt.2009.180430 · Cited by 52 · see citing works
Mayahi, L., Heales, S., Owen, D., Casas, J. P., Harris, J., MacAllister, R. J., & Hingorani, A. D. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.142257 · Cited by 49 · see citing works
Molecular Mechanisms Underlying Heart Failure and Their Therapeutic Potential
Fonseka, O., Gare, S. R., Chen, X., Zhang, J., Alatawi, N. H. O., Ross, C., & Liu, W. (2025) · Cells · doi:10.3390/cells14050324 · Cited by 50 · see citing works
Gliemann, L., & Hellsten, Y. (2019) · The Journal of Physiology · doi:10.1113/jp277056 · Cited by 47 · see citing works
Safety of sapropterin dihydrochloride (6r–bh4) in patients with pulmonary hypertension
Robbins, I. M., Hemnes, A. R., Simon Gibbs, J., Christman, B. W., Howard, L., Meehan, S., Cabrita, I., Gonzalez, R., Oyler, T., Zhao, L., et al. (2011) · Experimental Lung Research · doi:10.3109/01902148.2010.512972 · Cited by 47 · see citing works
Modeling of biopterin-dependent pathways of eNOS for nitric oxide and superoxide production
Kar, S., & Kavdia, M. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.06.009 · Cited by 42 · see citing works
Siu, K. L., Gao, L., & Cai, H. “. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.713149 · Cited by 42 · see citing works
Targeting endothelial and myocardial dysfunction with tetrahydrobiopterin
Moens, A. L., Kietadisorn, R., Lin, J. Y., & Kass, D. A. (2011) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2011.03.009 · Cited by 41 · see citing works
Regulation of Endothelial Cell Tetrahydrobiopterin
Harrison, D. G., Chen, W., Dikalov, S., & Li, L. (2010) · Advances in pharmacology · doi:10.1016/b978-0-12-385061-4.00005-2 · Cited by 40 · see citing works
Impaired Vasodilation and Nitric Oxide Synthase Activity in Glucocorticoid-Induced Hypertension
Mitchell, B. M., & Webb, R. C. (2002) · Biological Research For Nursing · doi:10.1177/1099800402004001003 · Cited by 38 · see citing works
Johnson, B. D., Mather, K. J., Newcomer, S. C., Mickleborough, T. D., & Wallace, J. P. (2012) · Cardiovascular Ultrasound · doi:10.1186/1476-7120-10-34 · Cited by 37 · see citing works
High-Salt Diet Increases Sensitivity to NO and eNOS Expression But Not NO Production in THALs
Ortiz, P. A., Stoos, B. A., Hong, N. J., Boesch, D. M., Plato, C. F., & Garvin, J. L. (2003) · Hypertension · doi:10.1161/01.hyp.0000047872.07864.20 · Cited by 34 · see citing works
Tănase, D. M., Apostol, A. G., Costea, C. F., Tărniceriu, C. C., Tudorancea, I., Maranducă, M. A., Floria, M., & Șerban, I. L. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14030534 · Cited by 34 · see citing works
McCarty, M. F. (2007) · Medical Hypotheses · doi:10.1016/j.mehy.2005.09.058 · Cited by 31 · see citing works
Yin, Y., Zhu, M., Wan, J., Zhang, C., Pan, G., Lu, J., Song, P., Chen, Y., Zhao, F.-R., Hai-ya, Y., et al. (2017) · Scientific Reports · doi:10.1038/srep43508 · Cited by 29 · see citing works
Bi, C. W. C., Xu, L., Tian, X. Y., Liu, J., Zheng, Y., Lau, C. W., Lau, D. T. W., Choi, R. C. Y., Dong, T. T.-X., Huang, Y., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051670 · Cited by 28 · see citing works
Chuaiphichai, S., Rashbrook, V. S., Hale, A., Trelfa, L., Patel, J., McNeill, E., Lygate, C. A., Channon, K. M., & Douglas, G. (2018) · Hypertension · doi:10.1161/hypertensionaha.118.11144 · Cited by 28 · see citing works
Oxidative stress, NADPH oxidases, and arteries
Sun, Q.-A., Madamanchi, N. R., & Runge, M. S. (2015) · Hämostaseologie · doi:10.5482/hamo-14-11-0076 · Cited by 28 · see citing works
- Authors
- Higashi, Y., Sasaki, S., Nakagawa, K., Fukuda, Y., Matsuura, H., Oshima, T., & Chayama, K.
- Affiliations
- Hiroshima University (JP)
- Corresponding author
- Higashi, Y.
- Venue
- American Journal of Hypertension
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-04-01
- Volume
- 15
- Issue
- 4
- Pages
- 326-332
- ISSN
- 0895-7061 (ISSN-L)
- 1941-7225
- OpenAlex
- W2028671428
- Cited by
- 173
- References
- 31
- Citations by year
- 2025: 5 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 6 · 2015: 9 · 2014: 9 · 2013: 11 · 2012: 18
- FWCI
- 2.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- tetrahydrobiopterin, BH4 supplementation, endothelium-dependent vasodilation, acetylcholine, forearm blood flow, essential hypertension, isosorbide dinitrate, nitric oxide synthase cofactor, endothelial function, forearm circulation
- MeSH terms
- Acetylcholine, Adult, Biopterins, Drug Synergism, Endothelium, Vascular, Female, Forearm, Humans, Hypertension, Male, Middle Aged, Nitric Oxide, Regional Blood Flow, Nitric Oxide Synthase, Nitric Oxide Synthase Type III
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