© Borgis - New Medicine 4/2003, s. 117-120
Kornelia Kedziora-Kornatowska1, Hanna Pawluk2, Tomasz Kornatowski3, Leszek Szadujkis-Szadurski3, Robert Pawluk2, Jolanta Czuczejko2, Jadwiga Motyl1, Jozef Kedziora2
Effect of perindopril on plasma carbonyl groups and the level of nitric oxide in elderly patients with essential hypertension
1 Department of Geriatrics, Rydygier Medical University, Bydgoszcz, Poland
Head: Kornelia Kedziora-Kornatowska, MD, PhD
2 Department of Biochemistry, Rydygier Medical University, Bydgoszcz, Poland
Head: Jozef Kedziora, MD, PhD
3 Department of Pharmacology, Rydygier Medical University, Bydgoszcz, Poland
Head: Leszek Szadujkis-Szadurski, MD, PhD
Introduction: The aim of the study was the measurement of the levels of nitric oxide and carbonyl groups in the plasma of elderly patients with essential hypertension.
Material and methods: Research was done on a control group of 18 healthy patients, and a group of 32 with essential hypertension patients. Prior pharmacological treatment, in case it was used, was stopped 2 days before the research was done. Then all of the patients with primary hypertension were applied perindopril in 4 mg/day dose for the period of 6 weeks. Patients with hypertension were tested after one week and 6 weeks since the start of perindopril therapy. Carbonyls formed by oxidation were determined by the Levine method.
The concentration of proteins in serum was analyzed using the burette method.
The nitrite concentration in plasma was analyzed by the Griess reaction according to Marlett et al.
Results: Hypertensive patients presented a statistically significant (p <0.001) higher carbonyl group concentration both before the therapy (0.25 ± 0.07 nmol/mg protein), and after 7 and 42 days (respectively 0.2 ± 0.08; 0.25 ± 0.07 nmol/mg protein) of perindopril application versus the control group (0.09 ± 0.02 nmol/mg protein). Hypertensive patients showed a lower NO level (1.47 ± 0.63 ?mol/l) compared to the control group (1.91 ± 0.60 ?mol/l), but this difference was not statistically significant.
Conclusions: The results show an increase in oxidative stress, and dysfunction of the vascular endothelium in eldery patients with hypertension
In recent years it has became more common to assume that reactive oxygen species (ROS) participate in both the ageing process and pathogenesis of various diseases of the eldesty age, including essential hypertension (1, 2, 3, 4). ROS have been proved to contribute to damage and dysfunction of vascular endothelium, hypertrophy of cells of vascular walls, and of smooth muscles. On of the main causes of all damage by ROS is the oxidation of both enzymatic and structural proteins. Carbonyl groups resulting from this process are one of the markers of increased oxidative stress (5, 6, 7). Another consequence of ROS activity in primary hypertension can be accelerated reduction of NO (8, 9). Indeed, both in the ageing process and in primary hypertension, vasorelaxation disorders related to endothelium damage have been observed as well as reduced production of NO in the endothelium. A hypothesis has been presented stating that endothelium dysfunction and reduced NO level may result from increased production of a superoxide anion radical. (10). Moreover, it has been observed that in elderly patients with primary hypertension, despite lower plasma renin activity, the activity of the local rennin-angiotensin-aldosteron system including vascular walls, increased. At the same time angiotensin II, playing a key role in the pathogenesis of hypertension, is a factor causing increased generation of ROS. The reaction between the superoxide anion radical and nitric oxide creates peroxynitrite, which is a strong oxidant initiating the peroxidation process (11). Inactive NO from the reaction with ROS and consequent dysfunction of the vascular endothelium can play a role in the pathogenesis of hypertension. The effects of antioxidant use can be observed particularly in elderly patients (12, 13). It is important to note that the activity of the vascular endothelium can be modulated by various pharmacological preparations. There are a few reports on oxidant stress modifying factors in elderly patients with intrinsic hypertension. Some hypertension medicines are reported to have encouraging effects (14, 15). However, it isn´t clear whether the results of these medicines are related to medicine´s hypertension mechanism and/or their modifying influence on certain metabolic processes.
The aim of the study was measurement of selected parameters of the oxygenic metabolism in the blood of elderly patients with arterial hypertension by measurement of the concentration of carbonyl groups in the proteins and concentration of nitric oxide (NO2-, NO3-) before and after treatment.
MATERIAL AND METHODS
The research was conducted on a control group of 18 healthy patients aged 65-96, and a group of 32 patients aged 65-96 with essential hypertension.The clinical characteristics of the patients are shown in Table 1. Research excluded patients declaring high alcohol consumption, addicted tobacco smokers, and those with diabetes, ischaemic heart disease, stroke history, kidney insufficiency, and other conditions of known free radical etiology. Prior pharmacological treatment, in case it was used, was stopped 2 days before the research was done. Then all of the patients with primary hypertension were applied perindopril in 4 mg/day dose for the period of 6 weeks. Patients were under the constant care of doctors in the Geriatric Clinic of the Medical Academy in Bydgoszcz. Hypertensive patients were tested after one week and 6 weeks from the start of perindopril therapy.
Table 1. Characteristics of study subjects.
|Parameters||Group I||Group II|
|Glucose, mg/dl||101,6 ? 9,8||76,4 ? 9,4|
|Cholesterol||223,4 ? 39,7||212,5 ? 37,9|
|HDL cholesterol, mg/dl||58,6 ? 3,4||47,8 ? 9,7|
|Trigliceride, mg/dl||113 ? 32,8||130,9 ? 49,5|
|Systolic pressure mmHg||119,3 ? 10,5||164,2 ? 15,4*|
|Diastolic pressure mmHg||71 ? 4,7||91,3 ? 6,8*|
|Creatinine, mg/dl||1,2 ? 0,4||1,05 ? 0,7|
* p <0,05 (group I vs groupII)
Carbonyls formed by oxidation were determined by the Levine method (16).
The concentration of proteins in serum was analysed using the burette method (17). The concentration of nitrites in serum was analysed by the Griess reaction according to Marlett et al (18).
Statistically significant higher systolic and diastolic blood pressures were observed in the group with hypertension in comparison with the normotensive group.
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