Research Article
Dynamic thiol/disulphide homeostasis in patients with newly diagnosed primary hypertension

https://doi.org/10.1016/j.jash.2015.12.008Get rights and content

Highlights

  • We aimed to determine dynamic thiol/disulphide homeostasis in primary hypertension (HT).

  • Thiol/disulphide balance was shown to shift toward disulphide form in HT group.

  • 24-hour systolic blood pressure and diastolic blood pressure displayed a positive correlation with disulphide or native thiol.

  • Disulphide or native thiol was determined as an independent risk factor for HT.

  • This suggests that abnormal thiol or disulphide may be associated with primary HT.

Abstract

We aimed to investigate the thiol/disulphide homeostasis in patients with newly diagnosed primary hypertension with a novel and automated method. Blood thiol/disulphide homeostasis, which consists of native thiol/disulphide exchanges, was investigated in 45 patients with primary hypertension and 45 healthy controls. The levels of native thiol, total thiol, and native thiol/total thiol ratio were lower while the disulphide level and disulphide/native thiol and disulphide/total thiol ratios were higher in patients with primary hypertension when compared with those in the control group. Positive correlation was detected between 24-hour systolic and diastolic blood pressure levels and disulphide/native thiol ratio. With reference to the stepwise multiple linear regression model; increase in disulphide/native thiol ratio and log(24-hour urine microalbumin) and decrease in native thiol/total thiol ratio are independent predictors of 24-hour systolic and diastolic blood pressure. This study demonstrated that thiol/disulphide homeostasis was shifted toward disulphide formation in patients with primary hypertension.

Introduction

According to the data of the World Health Organization, hypertension (HT) is the most common chronic disease (cardiovascular disease, chronic kidney disease, and cerebrovascular disease) that leads to death.1 Uncertainity of the etiopathogenesis of HT has continuously been a topic of interest for researchers. Recently, one of the topics on HT etiopathogenesis that has received great attention is; oxidative stress.

Oxidative stress occurs as a result of excessive production of free oxygen radicals and insufficiency of the antioxidant defense systems in comparison to the oxidant radicals.2 Reactive oxygen species (ROS) are the primary molecules responsible for oxidative damage.3 To protect the organism against the harmful effects of ROS, various enzymatic and nonenzymatic antioxidant mechanisms come into action. One of these antioxidant molecules are the thiols and these are the compounds containing sulfhydryl group which plays a critical role in preventing oxidative stress in cells.

The primary target of ROS is the thiol groups of sulphur containing amino acids (cysteine, methionine…) of proteins. The thiol groups in the media get oxidized by ROS forming reversible disulphide bonds. This conversion is the earliest sign of radical-mediated protein oxidation.4 The disulphide bonds so formed can again be reduced to thiol groups by a number of antioxidants. And in this way, thiol/disulphide homeostasis is maintained.

A number of experimental studies have demonstrated that abnormal thiol/disulphide homeostasis causes cellular proliferation or apoptosis.5, 6 Thiol/disulphide homeostasis has been measured since 1979 only in one direction,7 but with the novel method developed by Erel and Neselioglu, the levels of both variables can be measured separately as well as individually and collectively.8

To the best of our knowledge, thiol/disulphide homeostasis has not been measured by this novel method in HT patients in any study.

In this study, we aimed to investigate the levels of native thiol, total thiol and disulphide, and the ratios of disulphide/native thiol, disulphide/total thiol, and native thiol/total thiol in patients with newly diagnosed primary HT using a novel, automated method that determines dynamic thiol/disulphide homeostasis.

Section snippets

Study Population

This study was performed at Ankara Numune Training and Research Hospital, Internal Medicine Clinic, between April and July 2015.

Forty-five patients older than 18 years of age with newly diagnosed primary HT and not yet on treatment, and 45 healthy individuals were enrolled in the study. The secondary causes of HT were eliminated by medical history, physical examination, and laboratory measurements where necessary.

Patients with diabetes mellitus, acute-chronic kidney disease, proteinuria at

Results

The demographic characteristics and laboratory findings of the whole study population are shown in Table 1. Forty-five patients with a diagnosis of primary HT (mean age: 48.4 ± 9.2 years) and 45 healthy controls (mean age: 49.5 ± 10.6 years) were enrolled. The demographic characteristics including age, sex, and BMI were similar in the 2 groups.

The mean 24-h SBP and mean 24-h DBP of the hypertensive patients were higher when compared with those of the control group (P < .001).

The mean log(24-h

Discussion

In our study, thiol oxidation was determined to increase in primary HT patients compared with the control group and consequently dynamic thiol/disulphide homeostasis was determined to weaken. There was a positive correlation between disulphide/native thiol level and, 24-h SBP and 24-h DBP levels. According to the stepwise multiple linear regression model, the increase in disulphide/native thiol ratio and the decrease in native thiol/total thiol ratio were determined to be independent predictors

Conclusions

As a result, it was detected in our study that thiol/disulphide homeostasis declined in recently diagnosed primary HT patients compared with the control group. Decreased dynamic thiol/disulphide homeostasis was found to be associated with blood pressures, and disulphide/native thiol was determined as an independent risk factor for HT; thus, these suggest that abnormal thiol/disulphide homeostasis may be associated with HT etiopathogenesis. Further studies are required to clearly understand that

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    Funding: This study was not supported financially in the form of grants, equipment, drugs, or other.

    Conflict of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

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