Producción de radicales hidroxilo en sangre en pacientes ancianos hipertensos
Palabras clave:
HIPERTENSIÓN, RADICAL HIDROXILO, ANCIANOResumen
En el complejo y multicausal proceso que lleva a la hipertensión esencial, los radicales libres parecen jugar un papel clave, particularmente en la regulación local del lecho capilar. Además de la producción de ion superóxido en la célula endotelial, existen otros factores de producción de radicales libres, especialmente el radical hidroxilo, aun cuando la hipertensión esté medicada y clínicamente controlada.
Dado que si bien se han estudiado las defensas antioxidantes no se ha abordado todavía la generación de radicales libres en sangre en pacientes hipertensos, en el presente trabajo se estudió la producción del radical hidroxilo en sangre total en pacientes hipertensos controlados, mayores de 65 años, sin otra enfermedad y se compararon los niveles obtenidos con individuos de las mismas características, algunos de ellos hipertensos, que participaban en un programa de ejercicio y controlaban su dieta desde el punto de vista calórico. La producción del radical hidroxilo se determinó por la hidroxilación del salicilato, determinando la concentración del derivado 2,3 di-hidroxibenzoico (2,3-DHBA) por técnicas de cromatografía líquida de alta performance con detección electroquímica.
Las concentraciones de 2,3-DHBA luego de la interacción de la sangre con la molécula de salicilato en tubo fueron significativamente mayores en los pacientes hipertensos que en los individuos controles. En los individuos hipertensos que realizaban ejercicios se observó una tendencia a una menor producción de radicales hidroxilo.
De acuerdo con estos datos, la hipertensión esencial, aun medicada, se acompañaría de una producción elevada de radicales hidroxilo por los elementos formes de la sangre, que el ejercicio y la dieta tienden a disminuir. Aunque no podemos hablar de estrés oxidativo ya que no se determinó el estado de las defensas antioxidantes, es probable que estos radicales, si no son neutralizados, contribuyan a la enfermedad vascular que se observa en la hipertensión esencial. Estos resultados se ubicarían en la línea de investigación que propende a un control activo de la producción radicalaria aumentada en la hipertensión, además de la medicación antihipertensiva.
Citas
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2) Martignoni E, Blandini F, Godi L, Pacchetti C, Mancini F, Nappi G. Peripheral markers of oxidative stress in Parkinson's disease. The role of L-DOPA. Free Radic Biol Med 1999; 27(3-4): 428-37.
3) Sinclair AJ, Bayer AJ, Johnston J, Warner C, Maxwell SR. Altered plasma antioxidant status in subjects with Alzheimer's disease and vascular dementia. Int J Geriatr Psychiatry 1998; 13(12): 840-5.
4) Tubaro M, Cavallo G, Pensa V, Chessa MA, Natale E, Ricci R, et al. Demostration of the formation of hydroxyl radicals in acute myocardial infarction in man using salicylate as probe. Cardiology 1992; 80(3-4): 246-51.
5) Halliwell B. Reactive Oxygen Species and the Central Nervous System. J Neurochem 1992; 59(5):1609-23.
6) Floyd RA. Role of oxygen free radical in carcinogenesis and brain ischemia. FASEB J 1990; 4(9): 2587-97.
7) Zalba G, San José G, Moreno MU, Fortuño MA, Fortuño A, Beaumont FJ, et al. Oxidative stress in arterial hypertension. Role of NAD (P)H oxidase. Hypertension 2001; 38(6): 1395-9.
8) Kharbanda RK, Deanfield JE. Functions of the healthy endothelium. Coron Artery Dis 2001;12(6): 485-91
9) Landemmer U, Harrison DG. Oxidative stres and vascular damage in hypertension. Coron Artery Dis 2001; 12(6): 455-61.
10) Landmesse U, Harrison DG. Oxidant stress as a marker for cardiovascular events: Ox marks the spot. Circulation 2001; 104(22): 2638-40
11) Napoli C, Lerman L. Involvement of oxidation sensitive mechanisms in the cardiovascular effects of hypercholesterolemia. Mayo Clin Proc 2001; 76(6): 619-31.
12) Russo C, Olivieri O, Girelli D, Faccini G, Zenari ML, Lombardi S, et al. Anti-oxidant status and lipid peroxidation in patients with essential hypertension. J Hypertens 1998; 16(9): 1267-71.
13) Nakazono K, Watanabe N, Matasuno K, Sasaki J, Sato T, Inoue M. Does superoxide underlie the patogenesis of hypertension? Proc Natl Acad Sci 1991; 88(22): 10045-8.
14) Schneider R, Iscovitz H, Ilan Z, Bernstein K, Gros M, Iaina A. Oxygen free radical scavenger system intermediates in essential hypertensive patients before and immediately after sublingual captopril administration. Isr J Me. Sci 1990; 26(9): 491-5.
15) Parik T, Allikmets K, Tessalu R, Zilmer M. Oxidative stress and hyperinsulinaemia in essential hypertension: different facets of increased risk. J Hypertens 1996; 14(3): 407-10.
16) Kabi BC, Goel N, Rao YN, Tripathy R, Tempe A, Thakur, AS. Levels of erythrocyte malonyldialdehyde, vitamin E, reduced glutathione, G&PD activity and plasma urate in patients of pregnancy induced hypertension. Indian J Med Res 1994; 100: 23-5.
17) Swei A, Lacy F, Delano FA, Schmid-Schönbein GW. Oxidative stress in the Dahl hypertensive rat. Hypertension 1997; 30(6): 1628-33.
18) Vaziri ND, Wang XQ, Oveisi F, Rad B. Induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats. Hypertension 2000; 36(1): 142-6.
19) Romero-Alvira D, Roche E. High blood pressure, oxygen radicals and antioxidants: etiological relationships. Med Hypotheses 1996; 46(4): 414-20.
20) Alexander RW, Cooper T. Memorial Lecture. Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: a new perspective. Hypertension 1995; 25(2): 155-61.
21) Kristal B, Shurtz-Swirski R, Chezar J, Manaster J, Levy R, Shapiro G, et al. Participation of peripheral polymorphonuclear leukocytes in the oxidative stress and inflammation in patients with essential hypertension. Am J Hypertens 1998; 11(8 Pt 1): 921-8.
22) Zalba G, Beaumont J, San José G, Fortuño A, Fortuño MA, Diez J. Vascular oxidant stress: molecular mechanisms and pathophysiological implications. J Physiol Biochem 2000; 56(1): 57-64.
23) Fukai T, Siegfried MR, Ushio-Fukai M, Griendling KK, Harrison DG. Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension. Circ Res 1999; 85(1): 23-8.
24) Paolisso G, Tagliamonte MR, Rizzo MR, Manzella D, Gambardella A, Varricchio M. Oxidative stress and advancing age: results in healthy centenarians. J Am Geriatr Soc 1998; 46(7): 833-8.
25) De Angelis KL, Oliveira AR, Werner A, Bock P, Bello-Klein A, Fernández G, et al. Exercise training in aging: hemodynamic, metabolic, and oxidative stress evaluations. Hypertension 1997; 30(e Pt 2): 767-71.
26) Ji LL, Leeuwenburgh C, Leichtweis S, Gore M, Fiebig R, Hollander J, et al. Oxidative stress and aging. Role of exercise and its influences on antioxidant systems. Ann N Y Acad Sci 1998; 854: 102-17.
27) Rubanyi GM. Vascular effects of oxygen-derived free radicals. Free Rad Biol Med 1988; 4(2): 107-20.
28) Halliwell B, Kaur H. Aromatic hydroxylation of phenylalanine as an assay for hydroxyl radicals. Measurement of hydroxyl radical formation from ozone and in blood from premature babies using improved HPLC methodology. Anal Biochem 1994; 220(1): 11-5.
29) Halliwell B, Kaur H. Hydroxylation of salicylate and phenylalanine as assays for hydroxyl radicals: a Cautionary note visited for the third time. Free Rad Res 1997; 27(3): 239-44.
30) Floyd RA, Watson J, Wong PK. Sensitive assay of hydroxyl free radical formation utilizing high pressure liquid chromatography with electrochemical detection of phenol and salicylate hydroxylation products. J Biochem Biophys Methods 1984; 10(3-4): 221-35.
31) Floyd RA, Henderson R, Watson J, Wong PK. Use of salicylate with high pressure liquid chromatography and electrochemical detection (LCED) as a sensitive measure of hydroxyl free radical in Adriamycin treated rats. J Free Rad Biol Med 1986; 2(1): 13-8.
32) Halliwell B, Kaur H, Ingelman-Sundberg M. Hydroxylation of salicylate as an assay for hydroxyl radicals: a cautionary note. Free Rad Biol Med 1991; 10(6): 439-41.
33) Coudray C, Talla M, Martin S, Fatôme M, Favier A. High-performance liquid chromatography-electrochemical determination of salicylate hydroxylation products as an in vivo marker of oxidative stress. Anal Biochem 1995; 227(1): 101-11.
34) Grootveld M, Halliwell B. Aromatic hydroxylation as a potential measure of hydroxyl radical formation in vivo. Identification of hydroxylated derivatives of salicylate in human body fluids. Biochem J 1986; 237(2):499-504.
35) Tsai TH, Cheng FC, Hung LC, Chen CF. Measurement of hydroxyl radical in rat blood vessel by microbore liquid chromatography and electrochemical detection: an on-line microdialysis study. J Chromatogr B Biomed Sci Appl 1999; 734(2): 277-83.
36) Powell SR. Commentary. Salicylate trapping of OH as a tool for studying post-ischemic oxidative injury in the isolated rat heart. Free Rad Res 1994; 21(6): 355- 70.
37) Thome J, Zhang J, Davids E, Foley P, Weijers H-G, Wiesbeck GA, et al. Evidence for increased oxidative stress in alcohol-dependent patients provided by quantification of in vivo salicylate hydroxylation products. Alcohol Clin Exp Res 1997; 21(1): 82-5.
38) Kaur J, Edmonds SE, Blake DR, Halliwell B. Hydroxyl radical generation by reumatoid blood and knee joint synovial fluid. Ann Rheum Dis 1996; 55(12): 915-20.
39) Grootveld M, Halliwell B. 2, 3-Dihydroxybenzoic acid is a product of human aspirin metabolism. Biochem Pharmacol 1988; 37(2): 271-80.
40) Liu L, Leech JA, Urch RB, Silverman FS. In vivo salicylate hydroxylation: a potent biomarker for assesing acute ozone exposure and effects in humans. Am J Respir Crit Care Med 1997; 156(5): 1405-12.
41) Paterson JR, Blacklock C, Campbell G, Wils D, Lawrence JR. The identification of salicylate as normal constituent of serum: a link between diet and health? J Clin Pathol 1998; 51(7): 502-5.
42) Palumbo G, Carlucci G, Mazzeo P, Frieri G, Pimpo MT, Fanini D. Simultaneous determination of 5- aminosalicylic acid, acetyl-5-aminosalicylic acid and 2,5-dihydroxybenzoic acid in endoscopic intestinal biopsy samples in humans by high-performance liquid chromatography with electrochemical detection. J Pharm Biomed Anal 1995; 14(1-2): 175-80.
43) Narayan M, Berliner LJ, Merola AJ, Díaz PT, Clanton TL. Biological reactions of peroxinitrite: evidence for an alternative pathway of salicylate hydroxylation. Free Radic Res 1997; 27(1): 63-72.
44) Vernooij B, Uknes S, Ward E, Ryals J. Salicylic acid as a signal molecule in plant-pathogen interactions. Curr Opin Cell Biol 1994; 6(2): 275-9.
45) Yalpani N, Raskin I. Salicylic acid: a systemic signal induced plant disease resistance. Trends Microbiol 1993; 1(3): 88-92.
2) Martignoni E, Blandini F, Godi L, Pacchetti C, Mancini F, Nappi G. Peripheral markers of oxidative stress in Parkinson's disease. The role of L-DOPA. Free Radic Biol Med 1999; 27(3-4): 428-37.
3) Sinclair AJ, Bayer AJ, Johnston J, Warner C, Maxwell SR. Altered plasma antioxidant status in subjects with Alzheimer's disease and vascular dementia. Int J Geriatr Psychiatry 1998; 13(12): 840-5.
4) Tubaro M, Cavallo G, Pensa V, Chessa MA, Natale E, Ricci R, et al. Demostration of the formation of hydroxyl radicals in acute myocardial infarction in man using salicylate as probe. Cardiology 1992; 80(3-4): 246-51.
5) Halliwell B. Reactive Oxygen Species and the Central Nervous System. J Neurochem 1992; 59(5):1609-23.
6) Floyd RA. Role of oxygen free radical in carcinogenesis and brain ischemia. FASEB J 1990; 4(9): 2587-97.
7) Zalba G, San José G, Moreno MU, Fortuño MA, Fortuño A, Beaumont FJ, et al. Oxidative stress in arterial hypertension. Role of NAD (P)H oxidase. Hypertension 2001; 38(6): 1395-9.
8) Kharbanda RK, Deanfield JE. Functions of the healthy endothelium. Coron Artery Dis 2001;12(6): 485-91
9) Landemmer U, Harrison DG. Oxidative stres and vascular damage in hypertension. Coron Artery Dis 2001; 12(6): 455-61.
10) Landmesse U, Harrison DG. Oxidant stress as a marker for cardiovascular events: Ox marks the spot. Circulation 2001; 104(22): 2638-40
11) Napoli C, Lerman L. Involvement of oxidation sensitive mechanisms in the cardiovascular effects of hypercholesterolemia. Mayo Clin Proc 2001; 76(6): 619-31.
12) Russo C, Olivieri O, Girelli D, Faccini G, Zenari ML, Lombardi S, et al. Anti-oxidant status and lipid peroxidation in patients with essential hypertension. J Hypertens 1998; 16(9): 1267-71.
13) Nakazono K, Watanabe N, Matasuno K, Sasaki J, Sato T, Inoue M. Does superoxide underlie the patogenesis of hypertension? Proc Natl Acad Sci 1991; 88(22): 10045-8.
14) Schneider R, Iscovitz H, Ilan Z, Bernstein K, Gros M, Iaina A. Oxygen free radical scavenger system intermediates in essential hypertensive patients before and immediately after sublingual captopril administration. Isr J Me. Sci 1990; 26(9): 491-5.
15) Parik T, Allikmets K, Tessalu R, Zilmer M. Oxidative stress and hyperinsulinaemia in essential hypertension: different facets of increased risk. J Hypertens 1996; 14(3): 407-10.
16) Kabi BC, Goel N, Rao YN, Tripathy R, Tempe A, Thakur, AS. Levels of erythrocyte malonyldialdehyde, vitamin E, reduced glutathione, G&PD activity and plasma urate in patients of pregnancy induced hypertension. Indian J Med Res 1994; 100: 23-5.
17) Swei A, Lacy F, Delano FA, Schmid-Schönbein GW. Oxidative stress in the Dahl hypertensive rat. Hypertension 1997; 30(6): 1628-33.
18) Vaziri ND, Wang XQ, Oveisi F, Rad B. Induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats. Hypertension 2000; 36(1): 142-6.
19) Romero-Alvira D, Roche E. High blood pressure, oxygen radicals and antioxidants: etiological relationships. Med Hypotheses 1996; 46(4): 414-20.
20) Alexander RW, Cooper T. Memorial Lecture. Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: a new perspective. Hypertension 1995; 25(2): 155-61.
21) Kristal B, Shurtz-Swirski R, Chezar J, Manaster J, Levy R, Shapiro G, et al. Participation of peripheral polymorphonuclear leukocytes in the oxidative stress and inflammation in patients with essential hypertension. Am J Hypertens 1998; 11(8 Pt 1): 921-8.
22) Zalba G, Beaumont J, San José G, Fortuño A, Fortuño MA, Diez J. Vascular oxidant stress: molecular mechanisms and pathophysiological implications. J Physiol Biochem 2000; 56(1): 57-64.
23) Fukai T, Siegfried MR, Ushio-Fukai M, Griendling KK, Harrison DG. Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension. Circ Res 1999; 85(1): 23-8.
24) Paolisso G, Tagliamonte MR, Rizzo MR, Manzella D, Gambardella A, Varricchio M. Oxidative stress and advancing age: results in healthy centenarians. J Am Geriatr Soc 1998; 46(7): 833-8.
25) De Angelis KL, Oliveira AR, Werner A, Bock P, Bello-Klein A, Fernández G, et al. Exercise training in aging: hemodynamic, metabolic, and oxidative stress evaluations. Hypertension 1997; 30(e Pt 2): 767-71.
26) Ji LL, Leeuwenburgh C, Leichtweis S, Gore M, Fiebig R, Hollander J, et al. Oxidative stress and aging. Role of exercise and its influences on antioxidant systems. Ann N Y Acad Sci 1998; 854: 102-17.
27) Rubanyi GM. Vascular effects of oxygen-derived free radicals. Free Rad Biol Med 1988; 4(2): 107-20.
28) Halliwell B, Kaur H. Aromatic hydroxylation of phenylalanine as an assay for hydroxyl radicals. Measurement of hydroxyl radical formation from ozone and in blood from premature babies using improved HPLC methodology. Anal Biochem 1994; 220(1): 11-5.
29) Halliwell B, Kaur H. Hydroxylation of salicylate and phenylalanine as assays for hydroxyl radicals: a Cautionary note visited for the third time. Free Rad Res 1997; 27(3): 239-44.
30) Floyd RA, Watson J, Wong PK. Sensitive assay of hydroxyl free radical formation utilizing high pressure liquid chromatography with electrochemical detection of phenol and salicylate hydroxylation products. J Biochem Biophys Methods 1984; 10(3-4): 221-35.
31) Floyd RA, Henderson R, Watson J, Wong PK. Use of salicylate with high pressure liquid chromatography and electrochemical detection (LCED) as a sensitive measure of hydroxyl free radical in Adriamycin treated rats. J Free Rad Biol Med 1986; 2(1): 13-8.
32) Halliwell B, Kaur H, Ingelman-Sundberg M. Hydroxylation of salicylate as an assay for hydroxyl radicals: a cautionary note. Free Rad Biol Med 1991; 10(6): 439-41.
33) Coudray C, Talla M, Martin S, Fatôme M, Favier A. High-performance liquid chromatography-electrochemical determination of salicylate hydroxylation products as an in vivo marker of oxidative stress. Anal Biochem 1995; 227(1): 101-11.
34) Grootveld M, Halliwell B. Aromatic hydroxylation as a potential measure of hydroxyl radical formation in vivo. Identification of hydroxylated derivatives of salicylate in human body fluids. Biochem J 1986; 237(2):499-504.
35) Tsai TH, Cheng FC, Hung LC, Chen CF. Measurement of hydroxyl radical in rat blood vessel by microbore liquid chromatography and electrochemical detection: an on-line microdialysis study. J Chromatogr B Biomed Sci Appl 1999; 734(2): 277-83.
36) Powell SR. Commentary. Salicylate trapping of OH as a tool for studying post-ischemic oxidative injury in the isolated rat heart. Free Rad Res 1994; 21(6): 355- 70.
37) Thome J, Zhang J, Davids E, Foley P, Weijers H-G, Wiesbeck GA, et al. Evidence for increased oxidative stress in alcohol-dependent patients provided by quantification of in vivo salicylate hydroxylation products. Alcohol Clin Exp Res 1997; 21(1): 82-5.
38) Kaur J, Edmonds SE, Blake DR, Halliwell B. Hydroxyl radical generation by reumatoid blood and knee joint synovial fluid. Ann Rheum Dis 1996; 55(12): 915-20.
39) Grootveld M, Halliwell B. 2, 3-Dihydroxybenzoic acid is a product of human aspirin metabolism. Biochem Pharmacol 1988; 37(2): 271-80.
40) Liu L, Leech JA, Urch RB, Silverman FS. In vivo salicylate hydroxylation: a potent biomarker for assesing acute ozone exposure and effects in humans. Am J Respir Crit Care Med 1997; 156(5): 1405-12.
41) Paterson JR, Blacklock C, Campbell G, Wils D, Lawrence JR. The identification of salicylate as normal constituent of serum: a link between diet and health? J Clin Pathol 1998; 51(7): 502-5.
42) Palumbo G, Carlucci G, Mazzeo P, Frieri G, Pimpo MT, Fanini D. Simultaneous determination of 5- aminosalicylic acid, acetyl-5-aminosalicylic acid and 2,5-dihydroxybenzoic acid in endoscopic intestinal biopsy samples in humans by high-performance liquid chromatography with electrochemical detection. J Pharm Biomed Anal 1995; 14(1-2): 175-80.
43) Narayan M, Berliner LJ, Merola AJ, Díaz PT, Clanton TL. Biological reactions of peroxinitrite: evidence for an alternative pathway of salicylate hydroxylation. Free Radic Res 1997; 27(1): 63-72.
44) Vernooij B, Uknes S, Ward E, Ryals J. Salicylic acid as a signal molecule in plant-pathogen interactions. Curr Opin Cell Biol 1994; 6(2): 275-9.
45) Yalpani N, Raskin I. Salicylic acid: a systemic signal induced plant disease resistance. Trends Microbiol 1993; 1(3): 88-92.
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2004-03-31
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Dajas F, Ferrari A, Martínez A, Zeppi M, Ferreira M, Pintos Álvaro. Producción de radicales hidroxilo en sangre en pacientes ancianos hipertensos. Rev. Méd. Urug. [Internet]. 31 de marzo de 2004 [citado 7 de septiembre de 2024];20(1):12-8. Disponible en: https://revista.rmu.org.uy/index.php/rmu/article/view/927
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