© Borgis - New Medicine 4/2003, s. 121-124
Tomasz Kornatowski1, Kornelia Kedziora-Kornatowska2, Hanna Pawluk3, Jozef Kedziora3, Leszek Szadujkis-Szadurski1, Robert Pawluk3, Jolanta Czuczejko3, Jadwiga Motyl2
The influence of perindopril on lipid peroxidation and the oxidase activity of ceruloplasmin in the blood of old age patients with primary hypertension
1 Department of Pharmacology and Therapy, L. Rydygier Medical Academy of Bydgoszcz, Poland
Head: prof. Leszek Szadujkis-Szadurski, MD, PhD
2 Department and Clinic of Geriatrics, L. Rydygier Medical Academy of Bydgoszcz, Poland
Head: dr Kornelia Kedziora-Kornatowska, MD, PhD
3 Department of Biochemistry, L. Rydygier Medical Academy of Bydgoszcz, Poland
Head: prof. Jozef Kedziora, MD, PhD
Background: The purpose of this work was to estimate oxidase activity of ceruloplasmin and lipid peroxidation processes in the blood of elderly patients with primary hypertension. Furthermore, the influence of treatment with ACEi, perindopril, on the examined parameters was determined.
Material and methods: The research was carried out on 28 patients (65-91 yrs) with primary hypertension, treated with perindopril for 6 weeks, and normotensive persons who constituted the control groups: 25 (65-96 yrs – K1) and 23 (22-41 yrs – K2). The oxidase activity of ceruloplasmin was measured in serum by Ravin´s method, and the concentration of malondialdehyde (MDA) in erythrocytes according to Placer et al. Patients with hypertension underwent an examination after 7 days and 6 weeks from the beginning of therapy.
Results: It was found that in the group of patients with hypertension, the activity of ceruloplasmin was significantly higher in comparison to the activity in the control groups (K1 and K2). The concentration of MDA in erythrocytes of patients with hypertension was significantly higher than in the control groups (K1 and K2). In patients with hypertension, after 7 days of therapy a substantial decrease in the oxidative activity of ceruloplasmin was found, but the lowest value was observed after 6 weeks of therapy. These values were significantly lower than those from the control groups.
Conclusions: The results confirm the intensification of oxidative stress in elderly patients with primary hypertension and point to the beneficial antioxidant effect of perindopril.
Ageing and hypertension are essential factors in the risk of cardiovascular complications (1, 2). Such changes are significantly more intense in elderly patients with primary hypertension in comparison to persons of the same age but without hypertension (3, 4). In fact, an intensification of oxidative stress, which is the imbalance of pro-and antioxidative processes towards oxidation, is observed in the etiopathogenesis of both processes (5, 6). It has also been shown that reactive oxygen species play a significant role in the damage and dysfunction of vessel endothelium, and in hypertrophy and hyperplasia of cells of the vascular wall of smooth muscles (7, 8). Furthermore, it has been shown that one of the significant factors intensifying oxidative stress and also causing hypertrophy of the vascular wall and vascular contractility is angiotensin II. Angiotensin II released locally in the vascular wall plays a crucial role in the pathophysiology of hypertension (9). One of the possible action mechanisms of angiotensin converting enzyme inhibitors, apart from decreasing the level of angiotensin II and increasing the level of bradykinin, is an influence on oxidative stress in vessels. Research carried out by many authors has evaluated the antioxidative characteristics of various angiotensin convertase inhibitors by way of the influence on the activity of key cell antioxidative enzymes (superoxide dismutase, catalase, glutathione peroxidase), or the level of other antioxidants and lipid peroxidation products. However, such an influence on the activity of ceruloplasmin has not been evaluated (10, 11, 12).
The aim of this work was to evaluate the oxidase activity of ceruloplasmin and the process of lipid peroxidation in the blood of elderly patients with primary hypertension. In addition, the influence of treatment with angiotensin convertase inhibitor, perindopril, on the examined parameters was determined.
MATERIALS AND METHODS
The research was carried out on 25 healthy subjects (K1) between 65-96 years of age (average 74.3 ± 4.8 years) and on 23 healthy subjects (K2) between 22-41 years of age (average 37.4 ± 8.2 years), and on 28 persons between 65-91 years of age (average 74.7 ± 8.1 years) with 1st or 2nd level primary hypertension (according to the JNC-VI criteria and WHO/ISH recommendations) (13, 14).
The clinical characteristics of the examined persons are shown in table 1.
Table 1. The clinical characteristics of the examined persons.
|Parameter||Normotensive Subjects||Essential Hypertensive Patients (EAH)|
|Before treatment (EAH)||After treatment (EAH+P)|
|Number of subject||25||23||28||28|
|Age (y)||74.3 ? 4.8 ||37.4 ?
8.2a||74.7 ? 8.1 ||74.7 ? 8.1|
|Body mass index (kg/m2)||24.1? 2.1||22.6 ? 3.4||25,3 ? 2.8||24.9 ? 3.6|
|Systolic blood pressure (mmHg)||130.4 ? 6.7||118.7 ? 4.6||168.6 ?
10.4b||132.3 ? 6.4|
|Diastolic blood pressure (mmHg)||81.7 ? 8.4||74.6 ? 4.6||103.2 ?
10.4b||84.1 ? 8.5|
|Plasma glucose (mg/dl)||82.7 ? 4.9||79.1 ? 3.7||85.6 ? 5.5||88. 4 ? 6.8|
|Plasma total cholesterol (mg/dl)||190.6 ? 12.3||181.3 ? 9.6||196.7 ? 8.6||191.3 ? 10.6|
|Plasma HDL cholesterol (mg/dl)||43.4 ? 5.1||41.7 ? 7.3||42.6 ? 6.9||41.0 ? 5.6|
|Plasma LDL cholesterol (mg/dl)||109.3 ? 8.4||105.3 ? 7.2||110.3 ? 8.1||110.8 ? 9.6|
a p <0,05 (K2 vs K1, EAH, EAH+P)
b p <0,05 (EAH vs K1, K2, EAH+P)
A permit for carrying out this research was obtained from the local Bioethics Committee in the Medical University of Bydgoszcz (KB/53/2002/), as well as written agreements from the subjects.
The criterion for the division into normotensive participants and patients with hypertension was a pressure reading of <140/90 mmHg and = 140/90 mmHg consecutively. Secondary hypertension was ruled out by means of routine diagnostics. Two days before the research pharmacological treatment was stopped in patients who were having any, after which all patients with primary hypertension were administered perindopril at a dose of 2 or 4 mg per day during a period of 6 weeks.
Blood samples were taken from the basilic vein for coagulum and heparin. Subjects with hypertension were also examined after 7 days and after 6 weeks from the start of perindopril.
The oxidase activity of ceruloplasmin was measured in the serum by Ravin´s method (15). The concentration of malon dialdehyde (MDA) in red blood cells was measured by the Placer et al. method (16).
Statistical analysis of the results was made using an automated statistical analysis package, PC SSTAT V.4.0. A value of p <0.05 was considered statistically significant.
In the examined groups there were no statistically significant differences between gender, BMI, smoking history, glycaemia or plasma cholesterol levels. In addition, no statistically significant differences were found between the ages of the normotensive K1 group and the group of patients with hypertension (EAH).
Both K1 and EAH groups displayed a statistically significant difference in age in comparison to the group K2 normotensive.
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