Stickstoffmonooxid(NO)- und Arginin-Stoffwechsel und deren Bedeutung in der Männergesundheit

Zusammenfassung

Seit der Erstbeschreibung des „endothelium ­de­rived relaxing factor“ (EDRF) 1980 hat sich die Funktion des Endothels zu einem eigenen Forschungsgebiet entwickelt. Der wichtigste endotheliale Faktor ist das Stickstoffmonooxid (NO), das durch die NO-Synthase (NOS) aus der Vor­stufe L-Arginin gebildet wird. Störungen der Endo­thelfunktion spielen eine bedeutende Rolle in der Männergesundheit bei der Atherogenese und erektilen Dysfunktion und gehen den morphologischen Gefäßveränderungen voraus. Desweiteren spielt NO eine wichtige Rolle z. B. bei LUTS (Lower Urinary Tract Symptoms) und der männlichen Fertilität.

Abstract

Since the first description of the „endothelium-derived relaxing factor“ (EDRF) in 1980 the function of the endothelium has developed into a field of research of its own. The most important endothelial factor is nitric oxide (NO), which is formed from l-arginine with the help of NO synthase (NOS). Disturbances of the endothelial function play an important role in men’s health such as atherogenesis and erectile dysfunction and are also followed by morphological vessel changes. Furthermore, NO seems to play an important role in LUTS (lower urinary tract symptoms) and male fertility.

Schlüsselwörter

Stickstoffmonoxid - L-Arginin - Männergesundheit - Therapie für periphere Durchblutungsstörungen

Key words

nitric oxide - l-arginine - men’s health - peripheral vascular disease therapy

Literatur

• 1 Palmer R MJ, Ashton D S, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-Arginin.  Nature. 1988;  353 664-666
• 2 Lüscher T F, Haefeli W E. L-arginine in the clinical arena: Tool or remedy?.  Circulation. 1993;  87 1746-1748
• 3 Furchgott R F, Zawadzki J V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.  Nature. 1980;  288 373-376
• 4 Ignarro L J, Cirino G, Casini A et al. Nitric oxide as a signaling molecule in the vascular system: an overview.  J Cardiovasc Pharmacol. 1999;  43 879-886
• 5 Kröncke K D, Fehsel K, Kolb-Bachofen V. Inducible nitric oxide synthase and its product nitric oxide, a small molecule with complex biological activities.  Biol Chem. 1995;  376 327-343
• 6 Kröncke K D, Fehsel K, Kolb-Bachofen V. Inducible nitric oxide synthase in human disease.  Clin Exp Immunol. 1998;  113 147-156
• 7 Alderton W K, Cooper C E, Knowles R G. Nitric oxide synthase: structure, function and inhibition.  Biochem. 2001;  357 593-615
• 8 Baltrons M A, Pedraza C, Sardon T et al. Regulation of NO dependent cyclic GMP formation by inflammatory agents in neural cells.  Toxicol Lett. 2003;  139 191-198
• 9 Friebe A, Koesling D. Regulation of nitric oxide-sensitive guanylyl ­cyclase.  Circ Res. 2003;  93 96-105
• 10 Napoli C. Nitric oxide and atherosclerotic lesion progression: an overview.  J Card Surg. 2002;  17 355-362
• 11 Witte M B, Barbul A. Role of nitric oxide in wound repair.  Am J Surg. 2002;  183 406-412
• 12 Bon C L, Garthwaite J. On the role of nitric oxide in hippocampal long-term potentiation.  J Neurosci. 2003;  23 1941-1948
• 13 Bennett M R. Non-adrenergic non-cholinergic (NANC) transmission to the smooth muscle: 35 years on.  Prog Neurobiol. 1997;  52 159-195
• 14 Murphy S. Production of nitric oxide by glial cells: regulation and poten­tial roles in the CNS.  Glia. 2000;  29 1-14
• 15 Teerlink T, Neele S J, DeJong S et al. Estrogen replacement therapy lowers plasma levels of asymmetric dimethylarginine in healthy postmenopausal women.  Clin Sci. 2003;  105 67-71
• 16 Matsuguma K et al. Molecular mechanism for elevation of asymmetric dimethylarginine and its role for hypertension in chronic kidney disease.  J Am Soc Nephrol. 2006;  17 2176-2183
• 17 Hattori Y, Campell E B, Gross S S. Argininosuccinate synthase mRNA and activity are induced by immunostimulants in vascular smooth muscle cells. Role in the regeneration of arginin for nitric oxide synthesis.  J Biol Chem. 1994;  269 9405-9408
• 18 Nussler A K, Billiar T R, Liu Z Z et al. Coinduction of nitric oxide synthase and argininosuccinate synthetase in a murine macrophage cell line. Implications for regulation of nitric oxide production.  J Biol Chem. 1994;  269 1257-1261
• 19 Nussler A K, Liu Z Z, Hatakeyama K et al. A cohort of supporting meta­bolic enzymes in coinduced with nitric oxide synthase in human ­tumor cell lines.  Cancer Lett. 1996;  103 79-84
• 20 Closs E I, Scheld J, Sharafi M et al. Substrate supply for nitric-oxide synthase in macrophages and endothelial cells: Role of cationic amino acid transporters.  Mol Pharmacol. 2000;  57 68-74
• 21 Solomonson L P, Flam B R, Pendleton L C et al. The caveolar nitric oxide synthase / arginine regeneration system for NO production in endothelial cells.  J Exp Biol. 2003;  206 2083-2087
• 22 McDonald K K, Zharikow S, Block E R et al. A caveolar complex between the cationic amino acid transporter 1 and endothelial nitric oxide synthase may explain the “arginin paradox”.  J Bio Chem. 1997;  272 31213-31216
• 23 Moncada S, Higgs A. The L-Arginin-nitric oxide pathway.  N Engl J Med. 1993;  327 2002-2012
• 24 Vita J A, Treasure C B, Nabel E G et al. Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease.  Circulation. 1990;  81 491-497
• 25 Zeiher A M, Drexler H, Saurbier B et al. Endothelium-mediated coronary blood flow modulation in humans: effects of age, atherosclerosis, hyper­cholesterolemia and hypertension.  J Clin Invest. 1993;  92 652-662
• 26 Rubanyi G M, Romero J C, Vanhoutte P M. Flow-induced release of endothelium-derived relaxing factor.  Am J Physiol. 1986;  250 1145-1149
• 27 Moncada S, Palmer R MJ, Higgs E A. Nitric oxide: physiology, patho­physiology and pharmacology.  Pharmacol Rev. 1991;  43 109-142
• 28 Braun M, Wassmer G, Klotz T et al. Epidemiology of erectile dysfunction: results of the “Cologne Male Servey”.  Int J Impot Res. 2000;  6 305-311
• 29 Feldmann H A et al. Impotence and ist medical and psychosocial correlates: results of the Massachusetts Male Aging Study.  J Urol. 1994;  151 54-61
• 30 Montorsi P, Ravagnani P M, Galli S et al. Association between erectile dysfunction and coronary artery disease. Role of coronary clinical presentation and extent of coronary vessels involvement: the COBRA trial.  Eur Heart J. 2006;  27 2632-2639
• 31 Lonn E, Bosch J, Yusuf S HOPE and HOPE-TOO Trial Investigators et al.,. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial.  JAMA. 2005;  293 1338-1347
• 32 Shumaker S A, Legault C, Rapp S R et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women. The Women’s Health Initiative memory study: a randomized controlled trial.  JAMA. 2003;  289 2651-2662
• 33 Million Women Study Collaborators . Breast cancer and hormone-re­placement therapy in the Million Women Study.  Lancet. 2003;  362 419-427
• 34 Drexler H, Zeiher A M, Meinzer K et al. Correction of endothelial dysfunction in coronary microcirculation of hypercholesterolemic patients by L-arginine.  Lancet. 1991;  338 1546-1550
• 35 Creger M A, Gallagher S J, Girerd X J et al. L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans.  J Clin Invest. 1992;  90 1248-1253
• 36 Clarkson P, Adams M R, Powe A J et al. Oral L-arginine improves endothelium dependent dilation in hypercholesterolemic young adults.  J Clin Invest. 1996;  97 1989-1994
• 37 Cooke J P, Andron N A, Girerd X J et al. Arginine restores cholinergic ­relaxation of hypercholesterolemic rabbit thoracic aorta.  Circulation. 1991;  83 1057-1062
• 38 Cooke J P, Singer A H, Tsao P et al. Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit.  J Clin Invest. 1992;  90 1168-1172
• 39 Bode-Böger S M, Böger R H, Creutzig A et al. L-arginine infusion decreases peripheral arterial resistance and inhibits platelet aggregation in healthy volunteers.  Clin Sci. 1994;  87 303-310
• 40 Bode-Böger S M, Böger R H, Alfke H et al. L-Arginine induces NO-dependent vasodilation in patients with critical limb ischemia – a randomized controlled study.  Circulation. 1996;  93 85-90
• 41 Lerman A, Burnett J C, Higano S T et al. Long-term L-Arginin supplementation improves small vessel coronary endothelial function in humans.  Circulation. 1998;  97 2123-2128
• 42 Stanislavov R, Nikolova V, Rohdewald P. Improvement of erectile function with Prelox: a randomized, double-blind, placebo-controlled, crossover trail.  Int J Impot Res. 2007;  ,  [Epub ahead of print]
• 43 Klotz T, Mathers M J, Braun M et al. Effectiveness of oral L-arginine in first-line treatment of erectile dysfunction in a controlled crossover study.  Urol Int. 1999;  63 220-223
• 44 Ehren I, Adolfsson J, Wiklund N P. Nitric oxide synthase activity in the human urogenital tract.  Urol Res. 1994;  22 287
• 45 Bloch W, Klotz T, Loch C et al. Distribution of nitric oxide synthase implies regulation of circulation, smooth muscle tone and secretory function in the human prostate by nitric oxide.  The Prostate. 1997;  33 1-8
• 46 Takeda M, Tang R, Shapiro E et al. Effects of nitric oxide on human and canine prostates.  Urology. 1995;  45 440-446
• 47 Chung B H, Seung K C, Ki C C. Effects of nitric oxide on detrusor relaxation.  J Urol. 1996;  155 2090-2093
• 48 Müntener M, Schurch B, Wefer B et al. Systemic nitric oxide augmentation leads to a rapid decrease of the bladder outlet resistance in health men.  Uro Urol. 2006;  50 112-117
• 49 Klotz T, Matheus M J, Bloch W et al. Nitric oxide based influence of ­nitrates on micturition in patients with benign prostatic hyperplasia.  Int Urol Nephrol. 1999;  31 335-341
• 50 Lowe F C, James C K. Phytotherapy in treatment of benign prostatic ­hyperplasia: A critical review.  Urology. 1996;  48 12-20
• 51 Ehsan A, Sommer F, Schmidt A et al. Nitric oxide pathways in human bladder carcinoma. The distribution of nitric oxide synthases, soluble guanylyl cyclase, cyclic guanosine monophosphate and nitrothyrosine.  Cancer. 2002;  95 2293-2301
• 52 Huismann A, Vos I, van Faassen E E et al. Anti-inflammatory effects of tetrahydrobiopterin on early rejection in renal allografts: modulation of inductable nitric oxide synthase.  FASEB J. 2002;  16 1135-1137
• 53 de Lamirande E, O’flaherty C. Sperm activation: Role of reactive oxygen species and kinases.  Biochim Biophy Acta. 2007;  ,  [Epub ahead of print]
• 54 Ebisch I M, Thomas C M, Peters W H et al. The importance of folate, zinc and antioxidents in the pathogenesis and prevention of subfertility.  Hum Reprod Update. 2007;  13 163-174
• 55 Stanislavov R, Rohdewald P. Improvement of seminal parameters with Prelox: a randomized, double-blind, placebo-controlled, cross-over trial.  Phytother Res. 2009;  23 297-302