Associations of oxidative stress and inflammation and their role in the regulation of membrane fluidity of red blood cells in hypertensive and normotensive men: An electron spin resonance investigation

Kazushi Tsuda

Cardiovascular and Metabolic Research Center, Kansai University of Health Sciences, Osaka, Japan.

DOI: 10.4236/abb.2012.327124                

Abstract

There is evidence showing that increased levels of oxidative stress and C-reactive protein (CRP) might be associated with obesity, hypertension, atherosclerosis and other cardiovascular diseases. This study was undertaken to investigate possible relationships among plasma 8-iso-prostaglandin F2α (8-iso-PG F2α: an index of oxidative stress), high-sensitivity (hs)-CRP and membrane fluidity (a reciprocal value of microviscosity) in hypertensive and normotensive men using an electron spin resonance (ESR)-method. The order parameter (S) for the spin-label agents (5-nitroxide stearate) of red blood cell (RBC) membranes in the ESR spectra was significantly higher in hypertensive men than in normotensive men, indicating that membrane fluidity was decreased in hypertensive men. Both plasma 8-iso-PG F2α and hs-CRP levels were significantly increased in hypertensive men compared with normotensive men. In addition, plasma plasma 8-iso-PG F2α levels were correlated with plasma hs-CRP levels. In contrast, plasma nitric oxide (NO)-metabolites were lower in hypertensive men than in normotensive men, and inversely correlated with plasma 8-iso-PG F2α and hs-CRP. The order parameter(S) of RBCs was correlated with plasma 8-iso-PG F2α and plasma hs-CRP, and inversely correlated with plasma NO-metabolites, suggesting that reduced membrane fluidity of RBCs might be associated with increased oxidative stress, inflammation and endothelial dysfunction. Multivariate regression analysis also showed that, after adjusting for general risk factors, both plasma 8-iso-PG F2α and hs-CRP were significant determinants of membrane fluidity of RBCs. The ESR suggests that associations of oxidative stress and inflammation might have a close correlation with impaired rheologic behavior of RBCs and microcirculatory dysfunction in hypertensive men.

Keywords

Oxidative Stress; 8-Iso-Prostaglandin F2α; High-Sensitivity C-Reactive Protein; Nitric Oxide; Membrane Fluidity; Electron Spin Resonance; Hypertension

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Heistad, D.D., Wakisaka, Y., Miller, J., Chu, Y. and Pena-Silva, R. (2009) Novel aspects of oxidative stress in cardiovascular diseases. Circulation Journal, 73, 201-207. doi:10.1253/circj.CJ-08-1082
[2]	Schulz, E., Gori, T. and Munzel, T. (2011) Oxidative stress and endothelial dysfunction in hypertension. Hypertension Reseach, 34, 665-573. doi:10.1038/hr.2011.39
[3]	Rahsepar, A.A., et al. (2011) Prooxidant-antioxidant balance and antioxidized LDL antibody level values and cardiac function in patients with coronary artery disease. Cardiology, 122, 203-209. doi:10.1159/000339273
[4]	Whaley-Connell, A., McCullough, P.A. and Sowers, J.R. (2011) The oxidative stress in the metabolic syndrome. Review in Cardiovascular Medicine, 12, 21-29.
[5]	Dhawan, V. and Jain, S. (2004) Effect of garlic supplementation on oxidized low density lipoprotein and lipid peroxidation in patients of essential hypertension. Molecular and Cellular Biochemistry, 266, 109-115. doi:10.1023/B:MCBI.0000049146.89059.53
[6]	Rodrigo, R., et al. (2007) Relationship between oxidative stress and essential hypertension. Hypertension Research, 30, 1159-1167. doi:10.1291/hypres.30.1159
[7]	Vassalle, C., Botto, N., Andreassi, M. G., Berti, S. and Biagini, A. (2003) Evidence for enhanced 8-isoprostane plasma levels, as index of oxidative stress in vivo, in patients with coronary artery disease. Coronary Artery Disease, 14, 213-218. doi:10.1097/01.mca.0000063504.13456.c3
[8]	Wang, B., et al. (2006) Association of plasma 8-iso-prostane levels with the presence and extent of coronary stenosis in patients with coronary artery disease. Atherosclerosis, 184, 425-430.
[9]	Libby, P., Ridker, P.M. and Maseri, A. (2002) Inflammation and atherosclerosis. Circulation, 105, 1135-1143. doi:10.1161/hc0902.104353
[10]	Lagrand, W.K., et al. (1999) C-reactive protein as a cardiovascular risk factor: More than an epiphenomenon? Circulation, 100, 96-102.
[11]	Lloyd-Jones, D.M., Liu, K., Tian, L. and Greenland, P. (2006) Narrative review: Assessment of C-reactive protein in risk prediction for cardiovascular disease. Annals of Internal Medicine, 145, 35-42.
[12]	Venugopal, S.K., Devaraj, S., Yuhanna, I., Shaul, P. and Jialal, I. (2002) Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation, 106, 1439-1441. doi:10.1161/01.CIR.0000033116.22237.F9
[13]	Qamirani, E., Ren, Y., Kuo, L and Hein, T.W. (2005) C-reactive protein inhibits endothelium-dependent NO-mediated dilatation in coronary arterioles by activating p38 kinase and NAD(P)H oxidase. Arteriosclerosis, Thrombosis and Vascular Biology, 25, 995-1001. doi:10.1161/01.ATV.0000159890.10526.1e
[14]	Jarvisalo, M.J., et al. (2002) Elevated serum C-reactive protein levels and early arterial changes in healthy children. Arteriosclerosis, Thrombosis and Vascular Biology, 22, 1323-1328. doi:10.1161/01.ATV.0000024222.06463.21
[15]	Zicha, J., Kunes, J. and Devynck, M.A. (1999) Abnormalities of membrane function and lipid metabolism in hypertension. American Journal of Hypertension, 12, 315-331.
[16]	Tsuda, K. and Nishio, I. (2003) Membrane fluidity and hypertension. American Journal of Hypertension, 16, 259-261. doi:10.1016/S0895-7061(02)03257-0
[17]	Tsuda, K, Kimura, K., Nishio, I. and Masuyama, Y. (2000) Nitric oxide improves membrane fluidity of erythrocytes in essential hypertension: An electron paramagnetic resonance investigation. Biochemical and Biophysical Research Communications, 275, 946-954. doi:10.1006/bbrc.2000.3408
[18]	Tsuda, K., Kinoshita, Y., Kimura, K., Nishio, I. and Masuyama, Y. (2001) Electron paramagnetic resonance investigation on modulatory effect of 17β-estradiol on membrane fluidity of erythrocytes in postmenopausal women. Arteriosclerosis, Thrombosis and Vascular Biology, 21, 1306-1312. doi:10.1161/hq0801.093507
[19]	Tsuda, K., et al. (1987) Electron spin resonance studies of erythrocytes from spontaneously hypertensive rats and humans with essential hypertension. Hypertension, 9, III-19-III-24.
[20]	Tsuda, K., Kinoshita-Shimamoto, Y., Kimura, K. and Nishio, I. (2003) Nitric oxide is a determinant of membrane fluidity of erythrocytes in postmenopausal women: An electron paramagnetic resonance investigation. American Journal of Hypertension, 16, 244-248. doi:10.1016/S0895-7061(02)03261-2
[21]	Tsuda, K. (2010) Oxidative stress and membrane fluidity of red blood cells in hypertensive and normotensive men: An electron spin resonance investigation. International Heart Journal, 51, 121-124. doi:10.1536/ihj.51.121
[22]	Tsuda, K. (2012) Associations between high-sensitivity C-reactive protein and membrane fluidity of red blood cells in hypertensive elderly men: An electron spin resonance study. International Journal of Hypertension, 2012, Article ID: 292803. doi:10.1155/2012/292803
[23]	Le Sang Quan, K.H., Levenson, J., Del Pino, M., Simon, A. and Devynck, M.A. (1993) In vivo shear flow and erythrocyte membrane fluidity in hypertensive patients. British Journal of Clinical Pharmacology, 36, 437-443. doi:10.1111/j.1365-2125.1993.tb00392.x
[24]	Saldanha, C., et al. (1999) Impairement of the erythrocyte membrane fluidity in survivors of acute myocardial infarction. A prospective study. Clinical Hemorheology and Microcirculation, 20, 111-116.
[25]	Cazzola, R., Rondanelli, M., Russo-Volpe, S., Ferrari, E. and Cestaro, B. (2004) Decreased membrane fluidity and altered susceptibility to peroxidation and lipid composition in overweight and obese female erythrocytes. Journal of Lipid Research, 45, 1846-1851. doi:10.1194/jlr.M300509-JLR200
[26]	Loffredo, L., et al. (2007) Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease. European Heart Journal, 28, 608-612. doi:10.1093/eurheartj/ehl533
[27]	Annuk, M., Zilmer, M., Lind, L., Linde, T. and Fellstrom, B. (2001) Oxidative stress and endothelial function in chronic renal failure. Journal of American Society of Nephrology, 12, 2747-2752.
[28]	Zou, C.G., Agar, N.S. and Jones, G.L. (2001) Oxidative insult to human red blood cells induced by free radical initiator AAPH and its inhibition by commercial antioxidant mixture. Life Sciences, 69, 75-86. doi:10.1016/S0024-3205(01)01112-2
[29]	Lenfant, F., et al. (2000) Lidocaine inhibits potassium efflux and hemolysis in erythrocytes during oxidative stress in vitro. General Pharmacology, 34, 193-199. doi:10.1016/S0306-3623(00)00060-4