An increase of coronary artery disease has been observed in developing countries during the last years. Various factors may explain this accelerated increase. We propose that inappropriate diet and inadequate sanitary infrastructure may act as triggers to create an imbalance between nitric oxide (NO) and superoxide (O–2). An increase in the concentrations of oxidizedLDL produces both decreased NO and increased O–2 endothelial synthesis, by accumulation of asymmetrical NG-NG-dimethyl-L-arginine, the endogenous inhibitor of NO, and by activation of NAD(P)H oxidase. On the other hand, high rates of chronic infection-inflammation, due to inappropriate sanitary environment stimulate higher circulating levels of proinflammatory cytokines. These cytokines also contribute to reduced NO and increased O–2 endothelial production through the same mechanisms of oxidized LDL. The net result of this imbalance is an increased generation of peroxynitrate that injures the endothelium in a proatherogenic, prothrombotic and vasoconstrictive manner.

Keywords:
Cardiovascular disease, Dimethylarginine dimethylaminohydrolase, Endothelial dysfunction, Infection, Nutrition
1.
National Institute of Health, Lung and Blood Institute: Morbidity & Mortality: 1998 Chartbook on Cardiovascular, Lung and Blood Diseases. Bethesda, US Department of Health and Human Service, Public Health Services, 1998.
2.
Rosamond WD, Chambless LE, Folsom AR, Cooper LS, Conwill DE, Clegg L, Wang CH, Heiss G: Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994. N Engl J Med 1998;339:861–867.
3.
Christopher P, Howson C, Reddy S, Ryan T, Bale JR (eds): Control of Cardiovascular Diseases in Developing Countries. Washington, National Academy Press, 1998.
4.
Pabon Rodriguez A: La mortalidad en Colombia 1953–1991. Bogota, Instituto Nacional de Salud, 1993.
5.
Bautista L: Tendencias de la mortalidad por enfermedades cardiovasculares en Colombia y Santander, 1980–1996. ICIB, UIS, Panamerican Health Organization. Bucaramanga: 2000 September (Technical Report).
6.
Ministerio de Salud: III estudio nacional de salud bucal y II estudio de factores de riesgo de las enfermedades crónicas. Colombia, 1999.
7.
Panamerican Health Organization: Health Conditions in the Americas. Washington, PAHO Scientific Publication, 1994.
8.
Moncada S, Higgs EA, Hodson HF, Knowles RG, López-Jaramillo P, McCall T, Palmer RMS, Radomski MW, Rees DD, Schulz R: The L-arginine:nitric oxide pathway. J Cardiovasc Pharmacol 1991;17(S3):S1–S9.
9.
Ronson R, Nakamura M, Vinten-Johansen J: The cardiovascular effects and implications of peroxynitrite. Cardiovasc Res 1999;44:47–59.
10.
Leiper J, Vallance P: Biological significance of endogenous methilarginines that inhibit nitric oxide synthases. Cardiovasc Res 1999;43:542–548.
11.
Surdacki A, Nowicki M, Sandmann J, Tsikas D, Boeger RH, Bode-Boeger SM, Kruszelnicka-Kwiatkowska O, Kokot F, Dubiel JS, Froelich JC: Reduced urinary excretion of nitric oxide metabolites and increased plasma levels of asymmetric dimethylarginine in men with essential hypertension. J Cardiovasc Pharmacol 1999;33:652–658.
12.
Miyazaki H, Matsuoka H, Cooke JP, Usui M, Ueda S, Okuda S, Imaizumi T: Endogenous nitric oxide synthase inhibitor: A novel marker of atherosclerosis. Circulation 1999;99:1141–1146.
13.
Pettersson A, Hedner T, Milson I: Increased circulating concentrations of asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, in preeclampsia. Acta Obstet Gynecol Scand 1998;77:808–813.
14.
Creager MA, Gallagher SJ, Girerd XJ, Coleman SM, Dzau VJ, Cooke JP: L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. J Clin Invest 1994;90:1248–1253.
15.
Wolf A, Zalpour C, Theilmeier G, Wang BY, Ma A, Anderson B, Tsao PS, Cooke JP: Dietary L-arginine supplementation normalizes platelet aggregation in hypercholesterolemic humans. J Am Coll Cardiol 1997;29:479–485.
16.
Adams MR, Jessup W, Celermajer DS: Cigarette smoking is associated with increased human monocyte adhesion to endothelial cells: Reversibility with oral L-arginine but not vitamin C. J Am Coll Cardiol 1997;29:491–497.
17.
Schwarzacher SP, Lim TT, Wang B, Kernoff RS, Niebauer J, Cooke JP, Yeung AC: Local intramural delivery of L-arginine enhances nitric oxide generation and inhibits lesion formation after balloon angioplasty. Circulation 1997;95:1863–1869.
18.
Cooke JP, Dzau VJ: Derrangements of nitric oxide synthase pathway, L-arginine, and cardiovascular diseases. Circulation 1997;96:379–382.
19.
Vallance P, Leone A, Calver A, Moncada S: Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992;339:572–575.
20.
Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP: Novel mechanism for endothelial dysfunction: Dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 1999;99:3092–3095.
21.
Drewnowski A, Popkin BM: The nutrition transition: New trends in the global diet. Nutr Rev 1997;55:31–43.
22.
Moreano M: Perfil nutricional del Ecuador. CONADE/FAO. Ecuador 1998.
23.
Bautista L, Veral L, Pastora A: Prevalencia de Factores de Riesgo para Enfermedad Cardiovascular en Derecho Habientes de ECOPETROL. Residentes en Bucaramanga, 1999. Bucaramanga (Colombia): ECOPETROL/ Instituto Colombiano de Investigaciones Biomédicas; 2000 June (Technical report).
24.
Lang T: The public health impact of globalization of food trade; in Shetty PS, McPherson K (eds): Diet, Nutrition and Clinic Disease: Lessons from Contrasting Worlds. Chichester, Wiley, 1997, pp 173–187.
25.
Ohara Y, Peterson TE, Harrison DG: Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 1993;91:2546–5151.
26.
Nguyen-Khoa T, Massy ZA, Witko-Sarsat V, Canteloup S, Kebede M, Lacour B, Drueke T, Descamps-Latscha B: Oxidized low-density lipoprotein induces macrophage respiratory burst via its protein moiety: A novel pathway in atherogenesis? Biochem Biophys Res Commun 1999;262:804–809.
27.
World Bank: World Development Report: Investing in Health. New York, Oxford University Press, 1993.
28.
Teran E, Escudero C, Moya W, Flores M, Vallance P, Lopez-Jaramillo P: Elevated C-reactive protein and pro-inflammatory citokines in Andean women with preeclampsia. Int J Gynaecol Obstet 2001;75 (in press).
29.
Greer IA, Lyall F, Perera T, Boswell F, Macara LM: Increased concentrations of cytokines interleukin-6 and interleukin-1 receptor antagonist in plasma of women with preeclampsia: A mechanism for endothelial dysfunction? Obstet Gynecol 1994;84:937–940.
30.
Maseri A: Inflammation, atherosclerosis and ischemic events – exploring the hidden side of the moon. N Engl J Med 1997;336:1014–1016.
31.
Vallance P, Collier J, Bhagat K: Infection, inflammation and infarction: Does acute endothelial dysfunction provide a link? Lancet 1997;349:1391–1392.
32.
Hingorani A, Cross J, Kharbanda RK, Mullen MJ, Bhagat K, Taylor M, Donald AE, Palacios M, Griffin GE, Deanfield J, MacAllister R, Vallance P: Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation 2000;102:994–999.
33.
Bautista L, Lopez-Jaramillo P, Vera LM, Casas JP, Otero A, Guaracao AI: Is C-reactive protein an independent risk factor for essential hypertension? J Hypertens 2001;19:857–861.
34.
Tolando R, Jovanovic A, Brigelius-Flohe R, Ursini F, Maiorino M: Reactive oxygen species and proinflammatory cytokine signaling in endothelial cells: Effect of selenium supplementation. Free Rad Biol Med 2000;28:979–986.
35.
Volk T, Hensel M, Schuster H, Kox WJ: Secretion of MCP-1 and IL-6 by citokine stimulated production of reactive oxygen species in endothelial cells. Mol Cell Biochem 2000;206:105–112.
36.
National Center for Health Statistics: Current cigarette smoking by persons 18 years of age and over, according to sex, race, and age: United States, selected years 1965–94: United States, 1960–62, 1971–74, 1976–80, and 1988–91. Website: www.cdc.gov/nchs/datawh/statab/pubd/hus-t63h.htm.
37.
National Center for Health Statistics: Hypertension among persons 20 years of age and over, according to sex, race, and age: United States, 1960–62, 1971–74, 1976–80, and 1988–91. Website: www.cdc.gov/nchs/datawh/statab/pubd/hus-t69h.htm.
38.
Third Report on Nutrition Monitoring in the United States: Washington, Goverment Printing Office, 1995, vol I.
39.
Harris MI, Hadden WC, Knowler WC, Bennett PH: Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in US population aged 20–74 years. Diabetes 1987;36:523–534.
40.
American Heart Association: Physical Inactivity Biostatistical Fact Sheets. Dallas, AHA, 1999.
41.
National Center for Health Statistics: Overweight persons 20 years of age and over, according to sex, race, age and hispanic origin: United States, selected years 1965–94: United States, 1960–62, 1971–74, 1976–80, and 1988–91. Website: www.cdc.gov/nchs/datawh/statab/pubd/hus-t63h.htm.
© 2001 S. Karger AG, Basel
2001
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.