Differential Modulation of Markers of Oxidative Stress and DNA Damage in Arterial Hypertension

Abstract

Patients with arterial hypertension have an increased risk of developing tumors, particularly renal cell carcinoma. Arterial hypertension is linked to DNA damage via the generation of oxidative stress, in which an upregulated renin-angiotensin-aldosterone system plays a crucial role. The current study investigated surrogates of oxidative stress and DNA damage in a group of hypertensive patients (HypAll, n = 64) and subgroups of well (HypWell, n = 36) and poorly (HypPoor, n = 28) controlled hypertensive patients compared to healthy controls (n = 8). In addition, a longitudinal analysis was performed with some of the hypertensive patients. Markers for oxidative stress in plasma (SHp, D-ROM, and 3-nitrotyrosine) and urine (8-oxodG, 15-F_2t-isoprostane, and malondialdehyde) and markers for DNA damage in lymphocytes (γ-H2AX and micronuclei) were measured. In HypAll, all markers of oxidative stress except malondialdehyde were increased compared to the controls. After adjustment for age, this association was maintained for the protein stress markers SHp and 3-nitrotyrosine. With regard to the markers for DNA damage, there was no difference between HypAll and the controls. Further, no significant differences became apparent in the levels of both oxidative stress and DNA damage between HypWell and HypPoor. Finally, a positive correlation between the development of blood pressure and oxidative stress was observed in the longitudinal study based on the changes in D-ROM and systolic blood pressure. In conclusion, we found increased oxidative stress in extensively treated hypertensive patients correlating with the level of blood-pressure control but no association with DNA damage.

Keywords: 3-nitrotyrosine; 8-oxodG; SHp; high blood pressure; γ-H2AX.

Figure 1

Markers of oxidative stress and antioxidant potential measured in plasma and in urine. (A) Amount of SHp (free thiol groups in proteins) as a marker of antioxidant potential in plasma. (B) Quantification of D-ROM (derivatives of reactive oxygen species) as a marker of lipid oxidation in plasma. (C) Measurement of 3-nitrotyrosine as a marker of nitrosative stress to proteins in plasma. (D) Detection of the oxidative DNA base-pair modification 8-oxodG excreted in urine. Quantification of (E) MDA (malondialdehyde) and (F) 15-F_2t-IsoP (15-F_2t-isoprostane) as markers of lipid peroxidation in urine. Shown in each case is the comparison between the control group, HypWell, and HypPoor, with the p values inserted next to the standard deviation bar. The brackets indicate the comparison of HypAll to the control. n.s. = nonsignificant, * p ≤ 0.05, ** p < 0.01, and *** p < 0.001. Numbers over the boxplots indicate the number of patient samples analyzed.

Figure 2

Markers for DNA damage in lymphocytes. (A) γ-H2AX foci/nucleus, (B) micronuclei/1000 mononuclear cells, and (C) nuclear anomalies (NA)/1000 mononuclear cells in lymphocytes isolated from the participants’ blood samples. Shown in each case is the comparison between the control group, HypWell, and HypPoor. The brackets indicate the comparison of HypAll to control. n.s. = nonsignificant. Numbers over the boxplots indicate the number of samples analyzed.