Association of Microalbuminuria and IL-6, ET-1 and NO in Patients with Essential Hypertension

Author(s): Yuan Wang, Jianhui Tian, Yongchen Sun, Xiaxia Wang

Objective: Research had shown that hypertension was the main risk factor for coronary heart disease (CHD). Hypertension with microalbuminuria (MAU) is the important mark of target organ damage and endothelial function impaired, and also the independent factor for CHD. This paper aimed to explore the mechanism that patients with hypertension combined MAU increased the risk of CHD by investigating the relationship between MAU and IL-6, ET-1, NO in patients with essential hypertension (EH). Methods: To select 132 patients with essential hypertension who were hospitalized in the affiliated hospital of Qingdao university from October 2014 to July 2015. According to the MAU levels, there were 2 experimental groups in this experiment: MAU positive group (MAU>30 mg/l) and MAU negative group (MAU<30 mg/l). And 50 healthy persons in physical examination center of the same hospital were selected as a normal control group. All patients were performed blood routine, urinary routine, stool routine and biochemical analysis. IL-6 level and ET-1 level were measured by enzyme-linked immunosorbent assay. NO level was determined by nitrate reductase method. Statistical analysis was performed by SPSS version 19.0. Results: The serum IL-6 (103.45±4.89pg/ml), ET-1 (209.62±5.00pg/ml) and systolic blood pressure (174.59±25.75mmHg) levels in MAU positive group were obviously higher than that in the MAU negative group. The difference was statistically significant (P< 0.05). The serum NO level (19.76±2.48umol/l) in MAU positive group was significantly lower than that in the MAU negative group. The difference was statistically significant (P<0.05). The multi-factor regression analysis showed that the IL-6 (B=0.206, p=0.021), ET-1 (B=0.594, p<0.01), were positively correlated to MAU, while NO (B=-0.380, p=0.012) was negatively correlated to MAU. Conclusion: (1) The levels of IL-6 and ET-1 in hypertensive patients with MAU increased significantly, and the NO level decreased. (2) IL-6，ET-1 were positively correlated to MAU, while NO was negatively correlated to MAU. (3) Hypertension with MAU has important clinical significance. It needs more attention and effective management.

Essential hypertension, Microalbuminuria, Interleukin-6, Endothelin-1, Nitric Oxide, Coronary heart disease

1. Klausen K, Borch-Johnsen K, Feldt-Rasmussen B, et al. Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation 2004; 110:32-5.
2. Enayati S, Seifirad S, Amiri P, et al. Interleukin-1 beta, interferon-gamma, and tumor necrosis factor-alpha gene expression in peripheral blood mononuclear cells of patients with coronary artery disease. ARYA atherosclerosis, 2015, 11(5): 267
3. Al Shahi H, Shimada K, Miyauchi K et al. Elevated Circulating Levels of Inflammatory Markers in Patients with Acute Coronary Syndrome.Int J Vasc Med, 2015,805375.
4. Mahalle N, Garg M, Kulkarni M et al. Association of Inflammatory Cytokines with Traditional and Nontraditional Cardiovascular Risk Factors in Indians with known Coronary Artery Disease. Ann Med Health Sci Res, 2014, 4(5):706-712.
5. Mahfoud F，Ukena C，Poss J，et al．Microalbuminuria independently correlates to cardiovascular comorbidity burden in patients with hypertension. Clin Res Cardiol，2012，101(9):761-766．
6. DeckertT, Feldt-RasmussenB, Borch-Johnsenk, et al.Albuminuria refectswidespread vascular damage. The Steno hypothesis.Diabetologia, 1989, 32(4):219-26.
7. HoseiniVN, Rasouli M. Microalbuminuria correlates with thePrevalenceandseverityofcoronaryarterydiseaseinnon-diabeticpatients.Cardiol, 2009, 16(2):142-145.
8. Ekicibasi E,Kaderli AA, Kazazoglu AR, et al. Association of Microalbuminuriaandfasting insulin levels withpresenceandSeverity of coronary artery disease innon-diabetic cases.AnadoluKardiyolDerg,2008,8(1):16-21.
9. Oliveras A, Armario P, Sierra C et al. Urinary albumin excretion at follow-up predicts cardiovascular outcomes in subjects with resistant hypertension. Am J Hypertens, 2013, 26(9):1148-1154.
10. Hou H, Wang C, Sun F, et al. Association of interleukin-6 gene polymorphism with coronary artery disease: an updated systematic review and cumulative meta-analysis.Inflamm Res, 2015, 64(9):707-720.
11. Liu SL, Yin YW, Sun QQ et al. Genetic polymorphisms of interleukin-6 gene and susceptibility to coronary artery disease in Chinese population: Evidence based on 4582 subjects.Hum Immunol, 2015,76(7):505-510.
12. Caselli C, De Graaf MA, Lorenzoni et al. VHDL cholesterol, leptin and interleukin-6 predict high risk coronary anatomy assessed by CT angiography in patients with stable chest pain. Atherosclerosis, 2015, 241(1):55-61.
13. Kim KI，Lee JH，Chang HJ，et al．Association between blood pressure variability and inflammatory marker in hypertensive patient．Circulation,2008,72(2):293-298．
14. Gigante B, Strawbridge RJ, Velasquez IM et al. Analysis of the role of interleukin 6 receptor haplotypes in the regulation of circulating levels of inflammatory biomarkers and risk of coronary heart disease.PLoS One, 2015,10(3):e0119980.
15. Boutouyrie P, Tropeano AI, Asmar R, et al. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study. Hypertension 2002, 39(1):10-5.
16. Wang K, Dong PS, Zhang HF et al. Role of interleukin-6 gene polymorphisms in the risk of coronary artery disease [J].Genet Mol Res, 2015,14(2):3177-3183.
17. John R, Vane FRS, Erik E. Regulatory function of the vascular endothelium. The New England Tournal of Medicine, 1990, 323(1):27-36.
18. Funchgott RF，Zawadski JV．The obligatory role of endothelial cell in the relaxation of arterial smooth muscle by acetylcho line.Nature,1980, 288:373．
19. Mukai Y, Sato S. Polyphenol-containing azuki bean (Vigna angn-laris) extract attenuates blood pressure elevation and modulates nitric oxide synthase and caveolin-1 expressions in rats with hypertension.Nutr Metab Cardiovasc Dis. 2009,19(7):491-497.
20. Berényiová A, Kristek F, Drobná M,et al. Role of NO signaling pathway in regulation of vascular tone--new aspects. Cesk Fysiol, 2015,64(1):4-11.
21. Freitag DF, Butterworth AS, Willeit P et al. Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis.Lancet Diabetes Endocrinol, 2015, 3(4):243-253.
22. Colombo MG, Paradossi U, Andreassi MG, Botto N, et al. Endothelial nitric oxide synthase gene polymorphisms and risk of coronary artery disease. Clin Chem 2003, 49(3): 389-395.
23. Colombo MG, Andreassi MG, Paradossi U, Botto N, et al. Evidence for association of a common variant of the endothelial nitric oxide synthase gene (Glu298—>Asp polymorphism) to the presence, extent, and severity of coronary artery disease. Heart, 2002, 87(6): 525-528.
24. Wedgwood S，Black SM．Endothelin-1 decreases endothelial NOS expression and activity through ETA receptor mediated generation of hydrogen peroxide. Am J Physiol Lung Cell Mol Physiol, 2005, 288(3):L480-L487.