Effects of melatonin alone and in combination with aceten on chronostructure of diurnal hemodynamic rhythms in patients with hypertension stage II

AIM: To study effects of monotherapy with melatonin and combination melatonin + aceten on circadian pattern of hemodynamics in patients with essential hypertension stage II. MATERIALS AND METHODS: 20 EH patients were randomized into 2 groups, 10 patients each. Group 1 patients were given melatonin alone (6 mg at 22.00). Group 2 received aceten (25 mg at 18.00) and melatonin (6 mg at 22.00). Before treatment and after 10 days of it, hemodynamic parameters were measured each 3 hours for 24 hours. Arterial pressure was measured by Korotkov method, heart rate--by ECG R-R interval, stroke volume--by tetrapolar chest rheography according to Kubichek. Cardiac index, total and specific peripheral resistance, double product were estimated routinely. RESULTS: Internal and external dyssynchronism was registered in hemodynamic parameters of EH patients. Melatonin normalized circadian hemodynamic rhythms. It produced a hypotensive effect, reduced energy requirements of the myocardium. Combination of melatonin with aceten had a hypotensive and vasodilating effects but failed to restore circadian hemodynamic rhythms. CONCLUSION: Melatonin, epiphysial neurohormone, and its combination with aceten have hypotensive and vasodilating effects but melatonin monotherapy normalizes circadian hemodynamic rhythms while the combination was uneffective in this respect. This may be explained by interaction of melatonin and aceten actions.     

Comparative evaluation of the action of altiazem PP-180 taken at different time of the day by patients with stage-II hypertension

AIM: To study time-dependent effects of altiazem PP-180 and its influence on circadian pattern of hemodynamics in patients with essential hypertension stage II in its administration in 8.00, 14.00 and 22.00. MATERIAL AND METHODS: 30 patients with essential hypertension stage II (mean age 63.3 years) were divided into 3 groups 10 patients each by time of altiazem intake: 8.00, 14.00 or 22.00. Altiazem was given in a single daily dose 180 mg for 10 days. Before and after the treatment, a circadian profile of arterial pressure according to Korotkov was determined, 24-h monitoring of arterial pressure was made (AP-monitor Astrakard, Russia) and echo-CG measurements of hemodynamics were made (Toshiba, Japan). Tetrapolar chest rheography was also performed. RESULTS: More potent hypotensive effect of altiazem was observed in its administration in 8.00 and 22.00, less potent in 14.00. Negative chronotropic and positive inotropic effects occurred in its morning intake. These effects are less prominent in the evening and minimal if taken in 14.00. Normalization of circadian hemodynamic rhythms was registered in altiazem intake only in the morning. CONCLUSION: Altiazem PP-180 produces time-related hemodynamic effects.     

Pharmacologic correction of the adverse effects of beta-adrenoblockaders on the kidneys in patients with hypertension

Determination of the slow isoenzymes of carbon esterases (SICE) in the urine by the disc-electrophoresis techniques was used as a marker of kidney impairment in 90 patients with II stage essential hypertension. In obsidan and visken treatment the frequency of SICE detection in the urine has increased from 30-50 to 70-100 per cent; the effective renal blood flow was reduced and specific peripheral resistance was increased and leg blood flow deteriorated. Subsequent administration of trental. phentolamine and corinfar alleviated the unfavourable effect of beta-adrenoblockers, enhanced renal blood flow, decreased the frequency of SICE detection to the initial level and improved the results of treatment.     

Intrarenal hemodynamics and blood pressure in hypertensive patients with renal artery anomalies

AIM: To determine characteristics of a clinical course, 24-h profile of arterial pressure (AP), of renal hemodynamics, involvement of target organs in patients with arterial hypertension (AH) of the third degree and anomalies of renal arteries. MATERIAL AND METHODS: 24-h monitoring of AP, echocardiography, measurement of microalbuminuria, renal hemodynamic were made in 15 patients (9 female, 6 male) having resistant AH of the third degree and different anomalies of renal arteries (mean age 45.3 +/- 1.9 years). The control group consisted of patients with essential AH stage III (mean age 45.3 +/- 1.8 years). The groups were comparable by sex, age, duration of AH. RESULTS: The patients of the study group had a significantly lower pulsatility index in the renal artery and interlobular level and resistance index at the segmental and interlobular level of the RA on the side of the anomaly. There was a significantly higher minimal diastolic blood flow velocity in the segmental level of RA on the side of the anomaly. Renal scintigraphy revealed a decreased index of radiopharmaceutical accumulation. A positive correlation was found between the pulsatility index, resistance at a segment RA level and variability, an increase of morning diastolic blood pressure. The groups had significant differences neither by 24-h AP indices nor by severity of target organ lesion. CONCLUSION: Patients with RA anomalies have specific renal hemodynamics determining renal hypoperfusion on the side of the anomaly which may be involved in development of resistance to hypotensive therapy.     

Role of thyroid pathology in pathogenesis of arterial hypertension in diabetes

190 patients with diabetes mellitus (DM) were examined: 24 patients with DM type 1 and 166 with DM type 2. Frequency of arterial hypertension (AH) in diabetics is higher than in population. AH in different DM types varies by pathogenesis. Symptomatic renal AH is typical for DM1, essential AH combining with renal one in 1/3 of cases--for DM2. Treatment of AH and DM often provokes hypothyroidism which can be iatrogenic because of continuous intake of sugar reducing and antihypertensive drugs with antithyroid and strumogenic actions. Hypothyroidism aggravates an AH course: arterial pressure becomes high and resistant to hypotensive therapy. DM makes difficulties in selection of hypotensive drugs as many of them alter metabolism and due to negative attitude of the patients to continuous intake of sugar reducing, antihypertensive drugs, thyroid hormones. Therefore, hypertensive diabetics should be prepared for treatment psychologically and receive only prolonged hypotensive drugs. In DM with AH medication of choice is ACE inhibitors as they are nephroprotective, had no negative effect on carbohydrate, fat metabolism and thyroid system.     

Advantages of capoten chronotherapy of patients with hypertension in an outpatient setting

AIM: To compare the efficiency of a short course of preventive chronotherapy and traditional therapy with capoten in an outpatient setting. MATERIAL AND METHODS: Forty-two patients with stage II essential hypertension were divided into 2 groups: 20 controls were treated with capoten in a dose of 12.5-50 mg 3 times a day and 22 received capoten once a day in the same single dose 1.5-2 h before arterial pressure (AP) acrophase. Central hemodynamics was studied by echocardiography, regional hemodynamics by reheoencephalography before and at the end of therapy. RESULTS: In the control group AP normalized after capoten therapy in 3 patients, decreased by at least 10% but did not normalize in 9, and did not change in 8 patients. The results in the chronotherapy group were as follows: AP normalized in 5, decreased by at least 15% in 13, and did not change in 4 patients. Normalization of daily profiles of hemodynamic values and more favorable shifts in the cerebral bloodflow were more often seen in patients who received chronotherapy. CONCLUSION: Capoten chronotherapy of patients with essential hypertension, carried out in an outpatient setting, is obviously preferable to traditional treatment: no side effects were observed and a better hypotensive effect was attained with lower total dose.     

Obsidan treatment of neuroendocrine disorders and hyperkinetic syndrome in patients with macrofocal myocardial infarction

The trend in blood plasma adrenaline, noradrenaline, renin and parameters of central hemodynamics were studied in randomized sample of 67 patients with uncomplicated macrofocal myocardial infarction with a hyperkinetic syndrome. To 32 patients obsidan was administered intravenously (0.1 mg/kg), then orally for 2-3 days every 3-4 hours to lessen cardiac contraction rate by 20-30 per cent and to obtain moderate hypotension and after than 60-120 mg per 24 hours. The traditional treatment was prescribed to 35 patients of the control group. The acute period of the disease was marked by increased concentrations of catecholamines and renin and a close correlation between them and the central hemodynamic parameters. Use of obsidan led to a more rapid reduction and normalization of the content of biologically active substances, central hemodynamic parameters and to the removal of their correlation. The mechanisms of obsidan action are discussed.     

Cilazapril in the treatment of patients with arterial hypertension

Effects of monotherapy with cilazapril, cilazapril in combination with hydrochlorothiazide and the latter two drugs combination with verapamil (or obsidan) were studied in 20 patients with mild arterial hypertension (AH), moderate AH (n = 23) and severe AH (n = 22). Cilazapril was administered in a single daily dose of 2.5-5 mg for 24 weeks. Four measurements of arterial pressure, echocardiography, estimation of total cholesterol, triglycerides, glucose tolerance tests were made before the treatment and on its weeks 4, 12 and 24. Mono- and combined therapy with cilazapril proved effective in the above patients as it optimally lowered blood pressure and induced a reverse development of left ventricular hypertrophy. 24 week therapy with this drug has a positive effect on the level of triglycerides and postprandial glycemia.     

Cerebral perfusion in patients with arterial hypertension associated with type 2 diabetes

The aim of the study was to assess cerebral perfusion (CP) in patients with arterial hypertension in combination with type II diabetes. The subjects were 57 patients with stage II AH (mean age 51.6 +/- 5.7 years), among who there were 33 patients without disturbances in carbohydrate exchange and 24 patients with compensated or subcompensated type II diabetes. All the patients underwent single-photon emission computed tomography of the brain with 99m Tchexamethylpropyleneamineoxime. The study showed that patients suffering from AH with or without type II diabetes had signs of cerebral hypoperfusion and lowered cerebrovascular reserve even in the absence of focal neurological symptoms. Disturbances in cerebral perfusion were more prominent in patients suffering from AH with type II diabetes vs. patients without carbohydrate exchange disorder.     

Use of nebivolol in patients with mild and moderate hypertension

AIM: To evaluate the effectiveness and safety of the beta-adrenoblocker nebivolol in patients with mild and moderate essential hypertension. MATERIAL AND METHODS: The trial enrolled 20 patients. 11 of them had mild and 9 moderate arterial hypertension (mean age 47.1 +/- 9.52 years, hypertension history 6.98 +/- 2.75 years). 2-5 days after discontinuation of hypotensive drugs the examination was made including blood count, ECG, echocardiography, 24-h AP monitoring. It was repeated on days 56-60 of nebivolol therapy. Arterial pressure and heart rate were measured at the start of the treatment and 1, 3, 5 and 8 weeks later. RESULTS: Nebivolol treatment significantly reduced systolic arterial pressure in 30% and diastolic arterial pressure in 50% patients, heart rate decreased on the treatment day 7-10. On the treatment day 56-60 systolic and diastolic pressure lowered significantly in 53.3% and 66.7% patients, respectively. The analysis of changes in echocardiographic evidence found no significant shifts in volume and linear parameters. Nebivolol was well tolerated by 85% patients. Side effects included head ache, cardialgia, dizziness, weakness and nausea. CONCLUSION: Nebivolol (nebilet) is an effective hypotensive drug with mild side effects. Further studies on nebivolol effects on myocardial mass are needed.     

Effects of antihypertensive drugs with different mechanism of action on cardiac hemodynamics in patients with artificial pacemaker

Cardiohemodynamic effects of obsidan, nifedipin, captopril and prasosine were compared when the drugs were given in a 4-week course regarding circulation type and stimulation regime to 74 patients with artificial pacemaker suffering from mild or moderate essential hypertension. A peculiar action of obsidan, nifedipin and prasosine in cardiac pacing found at echocardiography is explained by the absence of frequency-dependent (chronotropic) cardiohemodynamic effects. Obsidan lowered blood pressure most effectively in hyperkinetic circulation. Nifedipine, captopril and prasosine were more potent in eu- and hypokinetic circulation. Reduction of arterial pressure by the above peripheral vasodilators in patients with hyperkinetic circulation results from a fall of total peripheral vascular resistance initially elevated by 16.5%, on the average. In isolated ventricular stimulation (regime VVI) vs atrial one (AAI regime) hypotensive action of the above drugs was more potent, but side effects were more frequent.     

Changes in blood rheological properties in patients with hypertension

AIM: To study hemorheology in patients with essential hypertension (EH), to improve EH treatment in terms of blood rheology. MATERIAL AND METHODS: Blood rheology, microcirculation, lipid plasm spectrum, central hemodynamics were studied in 90 patients with mild and 83 patients with moderate or severe EH as well as 30 healthy controls before and after treatment (hypotensive drugs, essential phospholipids, intravenous laser blood radiation, plasmapheresis). RESULTS: Hemorrheological disorders (subnormal deformability of the red cells and elastoviscosity of their membranes, disk-spherical transformation and hyperaggregation of blood cells, high dynamic viscosity) correlated with the disease severity, arterial pressure and total peripheral vascular resistance. Long-term (1-1.5 years) hypotensive therapy, especially with combination of beta-blockers with diuretics, has a negative effect on blood rheology. Optimisation of EH treatment in terms of blood rheology consists in using essential phospholipids in stable hypertension, intravenous laser radiation in complicated hypertension, plasmapheresis in drug-resistant hypertension. Such an approach not only significantly improves hemorheology but also provides good clinical and hypotensive effects in 75-80% patients. CONCLUSION: Blood viscodynamics should be taken into consideration in individual treatment of hypertensive patients.     

Risk of chronic renal failure in patients with non-insulin dependent diabetes mellitus with diabetic nephropathy and the stage of permanent proteinuria and arterial hypertension: role of clinical factors

AIM: To reveal prognostic factors which determine the risk of development of chronic renal failure (CRF) in patients with diabetes mellitus (DM) type II associated with diabetic nephropathy (DN) at the stage of continuous proteinuria in combination with arterial hypertension (AH). MATERIAL AND METHODS: A total of 60 AH patients suffering from type II DM with permanent proteinuria were examined. Chronic renal failure was registered in 21 patients. RESULTS: Among CRF patients, more frequent were males, high proteinuria and nephrotic syndrome, IHD, macroangiopathy of the lower limbs, VLDLP. CONCLUSION: Independent predictors of CRF in diabetes mellitus type II with AH and proteinuria were male gender, overweight, faster development of stable proteinuria from the time of diabetes diagnosis.     

Capozide-50 alone and in combination with melatonin in therapy of hypertension

Monotherapy with caposide-50 (C-50) was compared to combined therapy C-50 + melatonin in 22 patients with essential hypertension stage II (mean age 60 years). The patients were divided into two groups. Group 1 received C-50 at 8.00 a.m., group 2 received C-50 at 8.00 a.m. and melatonin at 10.00 p.m. in a dose 3 mg. Before the treatment and 14 days after it echo-CG was made to assess hemodynamics. Also, 24-h monitoring of arterial pressure was performed. The findings were analysed with variance statistics and cosinor-analysis. Group 1 achieved a moderate hypotensive effect. Circadian rhythm of systolic blood pressure was abnormal. Group 2 patients achieved more pronounced decline of systolic, diastolic and mean arterial pressures. Circadian rhythm of these pressure did not return to normal.     

Diovan effectiveness in combined treatment of severe arterial hypertension

AIM: To assess effectiveness of diovan, a novel angiotensin-II antagonist, in combined hypotensive treatment of patients with severe arterial hypertension. MATERIAL AND METHODS: 15 patients with severe arterial hypertension received diovan in a dose 80-160 mg/day for 8 weeks in combination with clofelin, beta-adrenoblockers, ACE inhibitors, diuretics prescribed before the start of diovan. Diovan effects were studied by 24-h monitoring of arterial pressure, tolerance, changes in blood counts, central hemodynamics. RESULTS: Adjuvant hypotensive treatment with diovan lowered arterial pressure to satisfactory levels in 80% of patients. 13.3% did not respond to diovan. 6.7% of patients were withdrawn because of allergy. Only 2 patients of those who completed the diovan course developed side effects in first two weeks of the treatment--they had head ache. CONCLUSION: Diovan is effective in combination with clofelin, ACE inhibitors, diuretics, beta-adrenoblockers.     

Comparative study of the effectiveness of Cozaar monotherapy and Cozaar and melatonin combined therapy in aged patients with hypertension

Effectiveness of Cozaar monotherapy (50 mg at 8 a.m.) was compared to that of Cozaar combination with melatonin (3 mg before sleep) in 21 patients with hypertension stage II (mean age 62 years). Clinical symptoms and hemodynamic parameters were evaluated with ECG and blood pressure monitoring. The findings were processed with statistical methods and Kosinor-analysis. Cozaar alone had moderate hypotensive and vasodilating effects, affected circadian rhythm of systolic and diastolic blood pressure, heart rate. Combination Cozaar + melatonin reduced blood pressure more noticeably, diminished cardiac output, energy consumption of the myocardium, normalized normal chronostructure of blood pressure and heart rate circadian rhythms.     

Effect of brerlipril in patients with non-insulin dependent diabetes mellitus and mild or moderate arterial hypertension as indicated by 24-h blood pressure monitoring]

AIM: To study a hypotensive effect of berlipril, an ACE inhibitor, using 24-h BP monitoring in patients with non-insulin-dependent diabetes mellitus (NIDDM) combined with stable mild or moderate arterial hypertension (AH). MATERIALS AND METHODS: 22 NIDDM patients with mild or moderate AH were treated with berlipril. 24-h monitoring of BP was made in all the patients before and 3 months after the treatment. RESULTS: A stable hypotensive effect of berlipril was achieved at its therapeutic dose 1.5 tablets a day once a day or divided into two doses a day. On treatment week 3-4 a hypotensive effect of berlipril enhanced in 5 patients. This may be due to ACE inhibitors action on the tissue component of the reninangiotensin system. CONCLUSION: Berlipril produces a high hypotensive effect and brings about a positive response of insulin-resistance in NIDDM associated with mild and moderate AH.     

Thiaside diuretics in combination with inhibitors of angiotensin-converting enzyme in patients with diabetes mellitus type 2 comorbid with arterial hypertension

AIM: To study the effect of co-renitek monotherapy for 16 weeks on parameters of 24-h monitoring of arterial pressure, carbohydrate, lipid, purin metabolism in patients with mild and moderate arterial hypertension (AH) and diabetes mellitus (DM) type 2. MATERIAL AND METHODS: 20 patients with DM type 2, mild or moderate AH received co-renitek (1-2 tablets a day) for 16 weeks. Before the treatment and 16 weeks later the patients were examined (24-h AH monitoring, carbohydrate, lipid, purin, electrolyte metabolism). RESULTS: Co-renitek treatment of DM type 2 patients with hypertension led to a significant lowering of mean systolic and diastolic pressure, improvement of 24-h AP profile and reduction of fasting glucose level. Co-renitek proved to be metabolically neutral in relation to lipid, purin and electrolyte metabolism. CONCLUSION: Co-renitek is effective and safe antihypertensive drug for treatment of arterial hypertension in patients with diabetes mellitus type 2.     

Evaluation of hypotensive and antiischemic effects of a combination of dihydropyridine and non-dihydropyridine calcium antagonists in patients suffering from coronary artery disease with arterial hypertension

The hypotensive and antiischemic activity of combined therapy with dihydropyridine group (amlodipine) and non-dihydropyridine group (verapamil retard) calcium antagonists (CA) as well as tolerance to this therapy were studied in 43 patients suffering from coronary heart disease (CAD) with II-III functional class exertional angina and II degree essential hypertension during 24 weeks. Twenty-four-hour ECG and blood pressure (BP) monitoring and Doppler EchoCG were done. The combination of amlodipine and verapamil retard in different day doses made it possible to achieve target BP levels in 86% of cases, improved circadian BP pattern and decreased left ventricular myocardial mass index (18.5% on the average; p < 0.01). The study also demonstrated prominent antiischemic and antianginal effects of the therapy, including patients with left ventricular hypertrophy. A decrease in myocardial ischemic (both painful and painless) episode frequency and the total duration of ST segment depression were the most pronounced changes. The combination of amlodipine and verapamil retard had a substantially lower rate of adverse effects compared with that of each of the component when used separately thanks to mutual neutralization of their side-effects or a possibility to lower their doses. Thus, the combination of CA from different groups possesses high hypotensive and antiischemic activity and good tolerance, which allows recommending it for treatment of patients suffering from CAD with arterial hypertension.     

The effect of prostenon on the pressor and depressor humoral systems in patients with resistant arterial hypertension

After ineffective combined drug therapy patients with the resistant patterns of arterial hypertension were given 3 to 5 intravenous injections of prostenon (prostaglandin E2) in the total dose 3-5 mg. Prostenon was noted to produce a lasting hypotensive effect in patients with resistant essential hypertension and parenchymatous renal hypertension. The patients manifested favourable changes in the general clinical symptomatology. The antihypertensive effect of prostenon was related to appreciable activation of depressor humoral factors, with activation of pressor humoral factors being less remarkable.