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Background: Plasma levels of soluble intercellular adhesion molecule 1 (sICAM-1) and monocyte chemoattractant protein 1 (sMCP-1) are associated with increased risk for future coronary events. However, the effect of statins on these inflammatory markers has hardly been studied. We analyzed whether treatment with the different doses of atorvastatin affects sICAM-1 and sMCP-1 plasma levels in subjects at high cardiovascular risk., Methods: Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration was a 12-week, prospective, multicenter, open-label trial that enrolled a total of 2117 subjects with coronary heart disease (CHD), CHD equivalent (defined as diabetes, peripheral vascular disease, or cerebrovascular disease), or a 10-year CHD risk >20%. Subjects with low-density-lipoprotein cholesterol between 100 and 220 mg/dL (2.6-5.7 mmol/L) and triglycerides <600 mg/dL (6.8 mmol/L) were assigned to atorvastatin (10-80 mg/d) based on low-density-lipoprotein cholesterol at screening. The Atorvastatin on Inflammatory Markers study included statin-free patients (N = 1078)., Results: At baseline, 52%, 14%, 12%, and 22% of subjects were assigned to doses of 10, 20, 40, and 80 mg, respectively. Levels of sICAM-1 [geometric mean (95% confidence interval); 283.8 (278.1-289.6) vs 131.9 (127.2-136.6) ng/mL, P < .0001] and sMCP-1 [164.1 (159.9-168.2) vs 131.1 (123.1-139.6 pg/mL, P < .0001] were increased in subjects at high cardiovascular risk compared to healthy subjects (n = 130). In the whole population, sICAM-1 and sMCP-1 levels were reduced by atorvastatin [% change (95% confidence interval); -2.2 (-3.8 to -0.6); -4.1 (-6.1 to -2); P = .006 and P = .0002, respectively]. All doses of atorvastatin diminished sICAM-1 and sMCP-1 levels in the highest quartile., Conclusions: Short treatment with atorvastatin reduced sICAM-1 and sMCP-1 plasma levels showing anti-inflammatory effects in subjects at high cardiovascular risk.

Objective: Increasing evidence indicates that the Fas/Fas ligand interaction is involved in atherogenesis. We sought to analyze soluble Fas (sFas) and soluble Fas ligand (sFasL) concentrations in subjects at high cardiovascular risk and their modulation by atorvastatin treatment., Methods and Results: ACTFAST was a 12-week, prospective, multicenter, open-label trial which enrolled subjects (statin-free or statin-treated at baseline) with coronary heart disease (CHD), CHD-equivalent, or 10-year CHD risk > 20%. Subjects with LDL-C between 100 to 220 mg/dL (2.6 to 5.7 mmol/L) and triglycerides < or = 600 mg/dL (6.8 mmol/L) were assigned to a starting dose of atorvastatin (10 to 80 mg/d) based on LDL-C at screening. Of the 2117 subjects enrolled in ACTFAST, AIM sub-study included the 1078 statin-free patients. At study end, 85% of these subjects reached LDL-C target. Mean sFas levels were increased and sFasL were reduced in subjects at high cardiovascular risk compared with healthy subjects. Atorvastatin reduced sFas in the whole population as well as in patients with metabolic syndrome or diabetes. Minimal changes were observed in sFasL., Conclusions: sFas concentrations are increased and sFasL are decreased in subjects at high cardiovascular risk, suggesting that these proteins may be novel markers of vascular injury. Atorvastatin reduces sFas, indicating that short-term treatment with atorvastatin exhibits antiinflammatory effects in these subjects.

Background: The third generation beta-blocker (carvedilol) is effective in reduction of hypertension, and of mortality and morbidity as a supplement to conventional drugs of heart failure therapies (diuretics, ACE inhibitors), based on randomized controlled trials and retrospective analysis., Objective: To analyse the efficacy of carvedilol in the treatment of heart failure with special focused on morbidity, mortality endpoints., Methods: We assessed the multicenter, randomised, double-blind studies involving more than 150 patients (1995-2005) from MEDLINE database, in which carvedilol was used in the case of moderate to severe heart failure. We also present the results of health-economic publications (2000-2005)., Results: In U.S. Carvedilol Heart Failure Study (n 1096) the mortality declined by 65% (3.2% vs. 7.8%; p <0.001) with carvedilol vs. placebo, while the cardiovascular hospitalization decline was 27% (14.1% vs. 19.6%; p = 0.036) in heart failure (LVEF < or = 5%) applied together with the basic therapy (diuretic and ACE-inhibitor). In the COPERNICUS trial the efficacy of carvedilol was compared to placebo in the case of severe HF patients (LVEF < 25%, n = 2889). The annual mortality risk declined by 35% (19.7% vs. 12.8%, 95% CI 19-48%, p = 0.00013) while the risk of mortality or any risk of hospitalisation by 24% (p = 0.00004) in the active group. The CAPRICORN study (LVEF < or = 0%, n=1959) showed that carvedilol is efficacious in reduction of total (HR: 0.77; 95% CI 0.60-0.98; p = 0.031) and cardiovascular mortality (HR: 0.75; 95% CI 0.58-0.96; p = 0.024) as far as high-risk patients are concerned., Conclusion: The effectiveness of carvedilol is certified in reduction of mortality and hospitalization in the treatment of moderate-severe heart-failure as part of the combination therapy. The benefits of use of the drug are well measurable not only on the level of patients but on the suppliers and the financer as well, thanks to the decline of resource utilization.

Background: End stage renal disease and hypertension are associated with higher cardiovascular mortality. Endothelial dysfunction plays an important role in the pathogenesis of cardiovascular diseases. The authors investigated the endothelium-dependent and -independent vasodilation in the forearm skin microcirculation and the plasma markers of endothelial damage in hypertensive hemodialysed patients and in normotensive control subjects., Methods: Laser Doppler flowmetry with iontophoresis of acetylcholine and sodium nitroprusside and the postocclusive reactive hyperemia test was performed in 22 normal control subjects and in 21 hemodialysed patients with hypertension. Levels of endothelin-1, big-endothelin, and von Willebrand Factor were measured, as well., Results: The average hyperemic response to the two doses of acetylcholine iontophoresis was 474 +/- 83%; 836 +/- 97% in the control subjects, and 160 +/- 26%; 360 +/- 67% in the hemodialysed patients group (p < 0.05). The vasodilation after the two doses of sodium nitroprusside was 381 +/- 60%, 782 +/- 81% in the control group and 186 +/- 42%; 379 +/- 63% in the dialysed patients group (p < 0.05 compared to control, respectively). The average peak flow during the postocclusive reactive hyperemia test was significantly lower in hemodialysed hypertensives (234 +/- 48%) compared to healthy control subjects (434 +/- 36%, p < 0.05). Levels of endothelin-1, big endothelin, von Willebrand Factor and von Willebrand Factor activity were significantly higher in the patient group compared to the control subjects., Conclusions: In hemodialysed hypertensive patients, both endothelium-dependent and -independent vasodilation are impaired. Markers of endothelial damage are elevated referring the progression of vascular disease.

Background: Uraemia and hypertension are associated with higher risk for cardiovascular complications. Endothelial dysfunction plays an important role in the pathogenesis of cardiovascular diseases. The aim of the present study was to evaluate endothelial function in the forearm skin microcirculation of patients with essential hypertension, in hypertensive haemodialysis patients and in normotensive control subjects., Methods: We performed laser Doppler flowmetry with iontophoresis of acetylcholine (ACh) and of sodium nitroprusside (SNP) as well as the post-occlusive reactive hyperaemia test (PORH) in 16 normal control subjects (CONT), in 16 patients with essential hypertension (EHT) and in 16 haemodialysis patients with essential hypertension (DHT). Plasma levels of endothelin-1, big-endothelin and von Willebrand factor (vWF) were also measured., Results: The average hyperaemic response to the higher dose of ACh iontophoresis was 801+/-110% in CONT, 563+/-69 % in EHT and 308+/-64% in DHT (P<0.05, between all comparisons). Vasodilation to the higher dose of SNP was 791+/-79% in CONT, 633+/-72% in EHT and 355+/-69% in DHT (NS, P<0.001 compared with controls, respectively). The average peak flow during PORH was significantly lower in both the EHT and DHT groups compared with controls (294+/-39, 267+/-59 and 429+/-45%, respectively, P<0.05). Levels of endothelin-1, big endothelin, vWF and vWF activity were significantly higher in the DHT group (P<0.05, compared with controls)., Conclusions: In hypertensive haemodialysis patients, both endothelium-dependent and -independent vasodilation was impaired. The observed increase in plasma markers of endothelial damage indicated a progression of vascular disease.

A 76-year-old man was admitted to our hospital with vertigo. Previously he had been extensively examined because of an increased erythrocyte sedimentation rate without any clinical symptoms. Physical examination revealed 60 mmHg blood pressure difference between the two arms. Color duplex ultrasound examination revealed bilateral extreme narrowing of the external carotid and axillobrachial artery with a dark, hypo-echoic halo around the lumen. This condition was recognized as a specific sign for giant cell arteritis (GCA), described originally in cases of temporal arteritis. The diagnosis was confirmed by biopsy of the temporal artery. In contrast to the typical cranial form of GCA -- our patient showed an unusual, bilateral large-vessel manifestation. The diagnosis was based on ultrasound images rather than on symptoms that characterize the well-known temporal form. This observation emphasizes the role of color duplex ultrasonography in the diagnosis and follow-up of GCA.

Background: Patient non-compliance is a significant contributor to poor blood pressure control. Although measures to improve compliance are known, they are not in routine use., Objective: To apply measures based on current recommendations in an integrated approach in the 'Manage it well!' (MIW) programme, and to determine the improvement in blood pressure control., Design and Setting: During the prospective open cohort study, 348 primary and 156 secondary care centres enrolled 6941 hypertensive patients and followed them for 6 months., Interventions: An integrated intervention package also applicable to everyday practice was introduced to improve treatment adherence, including education programmes for patients and physicians, tight follow-up with frequent office visits and regular home blood pressure measurements. Treatment was based on either trandolapril or verapamil SR with dose titration, with added-on therapy if necessary., Main Outcome Measure: Rates of control of blood pressure to < 140/90 mmHg., Results: Data were evaluated from 5468 patients, 72% known to have hypertension and 26% newly diagnosed [2% not available (n.a.)]. At baseline only 2.9% of treated patients had their hypertension well controlled (< 140/90 mmHg), but during the programme this increased to 40.9% (P < 0.001). The absolute reduction in office blood pressure was also significant (from 168 +/- 19/97 +/- 11 mmHg to 139 +/- 13/83 +/- 7 mmHg; P < 0.001). No differences in blood pressure control were found between trandolapril and verapamil SR regimens. Office blood pressure was greater than home blood pressure at baseline (168 +/- 19/97 +/- 11 mmHg compared with 151 +/- 17/89 +/- 10 mmHg; P < 0.001), but this difference disappeared at 6 months (139 +/- 13/83 +/- 7 mmHg compared with 140 +/- 13/84 +/- 7 mmHg, respectively)., Conclusions: The integrated, patient-focused approach used in the MIW programme significantly increases the success of treatment in a 'real-world' setting.

Aims: To investigate the effect of valsartan in the Valsartan-Heart Failure Trial (Val-HeFT) when added to angiotensin-converting enzyme inhibitor (ACEi) alone in patients with heart failure (HF)., Methods: Subjects in Val-HeFT receiving ACEi but not beta-blocker at baseline were analysed; 1532 were assigned to valsartan and 1502 assigned to placebo. Primary outcome events (all-cause mortality, hospitalisation for adjudicated heart failure, sudden death with resuscitation and need for >4 h of parenteral therapy for worsening heart failure) were monitored., Results: Mortality was not affected by valsartan but morbidity endpoints were significantly reduced (36.3% in placebo, 31.0% in valsartan, p=0.002) in patients receiving an ACEi but no beta-blocker. Quality of life (QOL) was significantly improved, ejection fraction (EF) significantly increased, left ventricular (LV) diameter significantly reduced and plasma B-type natriuretic peptide, norepinephrine and aldosterone levels significantly reduced with valsartan compared to placebo. The morbidity benefit was significant in patients on ACEi doses below the median (22% reduction, p=0.003) and not statistically significant in those receiving ACEi doses above the median (14% reduction, p=0.143)., Conclusion: Valsartan reduces heart failure hospitalisations and slows LV remodelling in patients treated with an ACEi in the absence of beta-blockade, particularly in those on lower doses of ACEi.

Unlabelled: In nonvalvular atrial fibrillation stroke prevention by anticoagulation is clearly recommended by evidence based medicine. Underusage of coumarin treatment however is a general problem. The aim of this study was the analysis of prehospital and hospital practice of anticoagulant therapy in a Hungarian cohort. 106 consecutive patients hospitalized in a Budapest medical department with chronic non-valvular atrial fibrillation were included. Mean age was 76 years, the percentage of males was 30%. High stroke risk factors were found in all patients, at least two of them in 72%. 70% of patients were 75 years old or more. Thus anticoagulant treatment was indicated in all patients, however at admission only 30% were anticoagulated, moreover therapeutic range was achieved in only 28% of them. At discharge in 77% of all patients and in 82% without contraindications coumarin treatment could be started, practically independently of age., Conclusions: In the Hungarian prehospital practice anticoagulant treatment of nonvalvular atrial fibrillation is underused and inefficient, but excellent rates even in international comparison can be achieved by adequate medical approach even in the elderly.

The aim of the study was to investigate the endothelium-dependent vasodilation in the forearm skin using two non-invasive laser Doppler applications in patients with essential hypertension (EHT) and in normotensive (NT) control subjects. The effect of two consecutive doses of acetylcholine (ACh) and that of sodium nitroprusside (SNP) on the skin microcirculation, and thereafter the postocclusive reactive hyperaemic (PORH) response, were measured in 25 patients with essential hypertension and also in 25 control normotensive healthy subjects. The plasma von Willebrand factor (vWF) level and activity were also determined. The average peakflow in PORH was 287 +/- 31.5% (x +/- S.E.M.) in EHT and 410.28 +/- 35.08% in NT (P < 0.01). The average hyperaemic response to the two doses of ACh-iontophoresis was 206.36 +/- 33.97 and 568.76 +/- 54.23% in EHT and 444.24 +/- 80.28 and 804.12 +/- 93.07% in NT (P < 0.01, 0.05). The response to SNP was similar in the two groups. The vWF levels were 122.5 +/- 13.2 and 89.6 +/- 8.1% (P = 0.0595, NS), the activities were 80.8 +/- 5.5 and 68.9 +/- 6.1% (P = 0.157, NS) in EHT and in NT, respectively. These results demonstrate that essential hypertension is associated with endothelial dysfunction in the skin microcirculation of the forearm.

Objectives: The primary objective was to assess the effects of rilmenidine monotherapy and in combination with perindopril on blood pressure (BP) in patients assessed with grade 1 or 2 essential hypertension. The study also examined the effects of 2-year rilmenidine monotherapy on left ventricular hypertrophy (LVH) and on diastolic function of the left ventricle, along with the effects of rilmenidine on left ventricular mass index in hypertensive patients with no LVH, and the relationship between BP reduction and any change in LVH., Research Design and Methods: Mild-to-moderate hypertensive patients (n = 500) were enrolled in a multicentre 2-year open study and treated with rilmenidine (1-2 mg per day) monotherapy or rilmenidine plus perindopril (2, 4 or 8 mg per day) if control of hypertension was not achieved with rilmenidine monotherapy within 12 weeks. Blood pressure was recorded at regular intervals by the investigators and LVH measured by centralised single-blind echocardiographic reading., Results: Rilmenidine monotherapy (average dose 1.42 mg) produced a significant decrease in BP from the baseline of 163 +/- 10/100 +/- 5 mmHg to 134 +/- 10/86 +/- 7 mmHg at 1 year and to 136 +/- 10/84 +/- 7 mmHg at 2 years (p < 0.001 for both). In 188 patients with LVH, the left ventricular mass index was significantly reduced from 161.4 +/- 30.5 to 131.3 +/- 26.5 at 1 year and to 134.1 +/- 26.0 g/m(2) at 2 years (p < 0.001 for both). Addition of perindopril to those patients whose BP was not normalised by rilmenidine monotherapy after 12 weeks further decreased BP significantly from 150 +/- 13/93 +/- 8 mmHg to 142 +/- 14/89 +/- 7 mmHg at the end of the 2nd year., Conclusions: Long-term rilmenidine monotherapy was shown to be efficient in controlling BP and in reducing LVH. The addition of perindopril to rilmenidine monotherapy proved to be effective and well tolerated in those patients who did not respond to rilmenidine alone.

The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multi-centre, prospective, randomized, double-blind, parallel-group study. The primary objective of SCOPE is to assess the effect of the angiotensin II type 1 (AT1) receptor blocker, candesartan cilexetil 8-16 mg once daily, on major cardiovascular events in elderly patients (70-89 years of age) with mild hypertension (DBP 90-99 and/or SBP 160-179 mmHg). The secondary objectives of the study are to test the hypothesis that antihypertensive therapy can prevent cognitive decline (as measured by the Mini Mental State Examination, MMSE) and dementia, and to assess the effect of therapy on total mortality, myocardial infarction (MI), stroke, renal function, and hospitalization. A total of 4964 patients from 15 participating countries were recruited during the randomization phase of SCOPE, exceeding the target population of 4000. The mean age of the patients at enrolment was 76 years, the ratio of male to female patients was approximately 1:2, and 52% of patients were already being treated with an antihypertensive agent at enrolment. The majority of patients (88%) were educated to at least primary school level. At randomization, mean sitting blood pressure values were SBP 166 mmHg and DBP 90 mmHg, and the mean MMSE score was 28. Previous cardiovascular disease in the study population included myocardial infarction (4%), stroke (4%) and atrial fibrillation (4%). Men, more often than women, had a history of previous MI, stroke and atrial fibrillation. A greater percentage of men were smokers (13% vs 6% in women) and had attended university (11% vs 3% of women). Of the randomized patients, 21% were 80 years of age. In this age group smoking was less common (4% vs 10% for 70-79-year-olds) and fewer had attended university (4% vs 7% for 70-79-year-olds). The incidence of MI was similar in both age groups. However, stroke and atrial fibrillation had occurred approximately twice as frequently in the older patients. The patients' mean age at baseline was similar in the participating countries, and most countries showed the approximate 1:2 ratio for male to female patients. There was also little inter-country variation in terms of mean SBP, DBP or MMSE score. However, there was considerable regional variation in the percentage of patients on therapy prior to enrolment.

Due to several mechanism, meals may modify the pharmacokinetics of drug products, thereby eliciting to clinically significant food interaction. Food interactions with the drug substance and with the drug formulation should be distinguished. Food interaction of different drug products containing the same active ingredient can be various depending on the pharmaceutical formulation technology. Particularly, in the case of modified release products, the food/formulation interaction can play an important role in the development of food interaction. Well known example, that bioavailability of theophylline can be influenced in different way (either increased, decreased or unchanged) by concomitant intake of food in the case of different sustained release products. The role and methods of food interaction studies in the different kinds of drug development (new chemical entity, modified release products, generics) are reviewed. Prediction of food effect response on the basis of the physicochemical and pharmacokinetic characteristics of the drug molecule or formulations is discussed. The results of three food interaction studies carried out the products of EGIS Pharmaceuticals Ltd. are also reviewed. The pharmacokinetic parameters of theophyllin 400 mg retard tablet were practically the same in both fasting condition and administration after consumption of a high fat containing standard breakfast. The ingestion of a high fat containing breakfast, increased the AUC of nifedipine from 259.0 +/- 101.2 ng h/ml to 326.7 +/- 122.5 ng h/ml and Cmax from 34.5 +/- 15.9 ng/ml to 74.3 +/- 23.9 ng/ml in case of nifedipine 20 mg retard tablet, in agreement with the data of literature. The statistical evaluation indicated significant differences between the pharmacokinetic parameters in the case of two administrations (before and after meal). The effect of a high fat containing breakfast for a generic version of buspiron 10 mg tablet and the bioequivalence after food consumption were studied in a single-dose, three-way (test and reference products administered after consumption of standard breakfast, as well as test product in fasting condition), cross-over, food effect bioequivalence study. According to the results, the test product--which, in a former study proved to be bioequivalent with the reference product in fasting state--is bioequivalent with the reference product under feeding conditions and the food intake influenced the pharmacokinetics of the test tablets.

After the brief description of the most important hypertensive pathophysiological processes (renin, angiotensins) which are closely related to angiotensin converting enzyme (ACE) inhibitors as well as to the mechanisms of action of captopril, author summarizes the essential clinical findings from the international and Hungarian literature. A short guideline for the administration of captopril to hypertensive patients is also given.

A clinical pharmacokinetic bioequivalence study with two retard filmtablet preparations, both containing 20 mg of nifedipine (CAS 219829-25-4) was carried out. The investigated test preparation was Cordaflex 20 mg retard filmtablet. The pharmacokinetic parameters were determined after single and repeated administration in 15 and 16 healthy male volunteers, respectively, in open, randomised studies of cross-over design. Plasma levels of nifedipine were determined by HPLC with electrochemical detection using a robotic sample preparation technique. Statistical comparison of the pharmacokinetic parameters (AUC0-infinity, AUCss, tau tmax, Cmax, Css,min, Css,av, MRT, etc.) calculated from plasma concentration-time curves by ANOVAlog, confidence interval, Schuirman's, Westlake's, Anderson's and Wilcoxon's tests, furthermore the comparison of the clinical results did not show any significant difference between the two preparations. It is concluded that the two preparations are bioequivalent after repeated administration.

The efficacy and safety of the HMG-CoA reductase fluvastatin was investigated in a multicenter, open label clinical therapeutic trial in the treatment of hypercholesterinaemia in hypertensive patients (WHO I-II.). 49 patients were involved, 6 patients were dropped out because of th lack of compliance, 43 patients were investigated (mean age: 57.6 +/- 9.4 years, mean blood pressure: 146 +/- 16/88+/- g mmHg (systolic/diastolic). The antihypertensive treatment was unchanged during the study. An 8 weeks low-lipid diet was started if the fasting total cholesterol (TC) level was equal or higher than 6.5 mM/L and the triglyceride level was lower than 4.6 mM/L. After the dietary period fluvastatin treatment was started (20 mg o.d.), if the level of LDL-C was higher than 4,1 mM/L. Blood pressure, heart rate, TC, HDL-C (HDL2-C, HDL3-C), apoA1, apoB, TG were measured at the 4th, 8th, 12th weeks of treatment. LDL-C was calculated with Fridewald equation. The daily dose of fluvastatin was increased to 40 mg, if LDL-C level was higher than 3.5 mM/L after 4 weeks of treatment. 36 patients completed the study (Group B). 7 patients were dropped out at the end of the dietary period, because of the significant decrease of TC and LDL-C levels (Group A). In Group B fluvastatin significantly reduced the level of TC (from 7.22 +/- 0.88 to 5.99 +/- 0.98 mM/L), of LDL-C (from 5.13 +/- 0.71 to 3.95 +/- 0.88 mM/L), and the level of ApoB (from 0.97 +/- 0.26 to 0.85 +/- 0.15 mM/L), but did not influence significantly the level of HDL-C, ApoA1 and TG. The diastolic blood pressure decreased significantly during the dietary period, while after beginning the fluvastatin treatment the decrease of the systolic blood pressure became significant. There was no change in the heart rate. Only minor side effects were observed in 3 patients (dysuria, constipation, lack of appetite). Fluvastatin proved to be an effective and well-tolerated drug in the treatment of hypercholesterinaemia in hypertensive patients.

Comparative pharmacokinetic studies have been carried out with two 20 mg nifedipine active substance-containing retard film coated tablets, Cordaflex produced by EGIS Pharmaceuticals Co., Ltd. and Adalat of Bayer AG. The pharmacokinetic parameters and the relative bioavailability were determined in 15 and 16 healthy male volunteers, respectively after single and repeated administration in open, randomized cross over study. The plasma concentration of nifedipine was determined by HPLC-ED method, using laboratory robot for automated sample preparation. On the basis of graphical and statistical comparison of the pharmacokinetic parameters (AUC0-infinity, AUCss,0-tau, tmax, Cmax, Css,min, Css,av, MRT, etc.) calculated from the time-plasma concentration curve, moreover on the basis of clinical results, there was no significant difference between the two preparations. In conclusion, the relative bioavailability of Cordaflex and Adalat 20 mg retard tablets did not show significant difference after single and repeated administration.

These are the preliminary data of an open multicenter trial of antihypertensive treatment with isradipine as monotherapy (dose, 4.55 +/- 0.56 mg twice daily; n = 11) or isradipine (7.5 +/- 0.63 mg twice daily) in combination with bopindolol (1.16 +/- 0.12 mg once daily; n = 30) administered for 3 years to patients with essential hypertension (WHO classification I or II). Blood pressure was significantly decreased in both treatment groups and there was no indication of resistance to therapy. Plasma levels of total cholesterol and triglycerides were decreased by the end of the second year of treatment, and there was a tendency toward increase in plasma levels of high-density lipoprotein cholesterol (HDL2 or HDL3). The atherogenic index (ratio between total cholesterol and HDL2 plus HDL3) was also decreased. Blood glucose levels remained unchanged in both normoglycemic patients and those with non-insulin-dependent diabetes mellitus (NIDDM) during 3 years of therapy. It is concluded that isradipine is safe and effective when administered long-term in the treatment of hypertensive patients with either hyperlipidemia or NIDDM.

The hypothesis that plasma lipids may modulate the antihypertensive effect of the calcium antagonist isradipine was tested in 85 patients who had essential hypertension. Significant linear correlations were found between the antihypertensive effect of isradipine and plasma levels of total cholesterol and high-density lipoprotein (HDL2 or HDL3) in normotriglyceridemic (n = 63), but not in hypertriglyceridemic (n = 22), patients. From this, we conclude that normal levels of plasma lipids may modulate the function of calcium channels and their interaction with calcium antagonists.

The "white coat effect" has been investigated by non-invasive automatic blood pressure monitoring in patients with hypertension, defined by casual blood pressure readings. A significant "white coat effect" has been demonstrated in 30 (32%) of the 93 patients: the average values were 17/9 mmHg and 6 beat/min, the highest values were 37/29 mmHg and 13 beat/min. The examination has been repeated after 24 hours in 11 cases and the phenomenon was reproducible. The "white coat effect" did not disappear even when the changes were compared to the averages of three subsequent automatic blood pressure measurements. There were significantly more women, than men among the "white coat" positive patients. However, no difference was found in age, occupation and the known duration of hypertension. Neither was any correlation between the "white coat effect" and the blood pressure reaction to mental arithmetic test. It is emphasized that the casual readings can significantly overestimate the blood pressure. This finding must be considered especially in the diagnosis of borderline hypertension.

The central alpha-2-adrenergic receptor agonist, clonidine (300 micrograms daily) significantly increased the plasma beta-endorphin-like immunoreactivity (beta ELI) in 12 patients with mild to moderate essential hypertension in a randomized, crossover study. A significant linear correlation between the increase in plasma beta ELI and the decrease in blood pressure (both systolic and diastolic) was found after clonidine administration. The role of the reduced central sympathetic tone, induced by alpha-2-adrenoceptor stimulation, in the elevation of circulating beta ELI can be suggested. The plasma beta ELI increased also significantly after the dopaminergic D-2 receptor agonist, bromocryptine treatment, (5 mg, daily) in 13 patients with borderline and mild essential hypertension in a randomized, crossover study. A significant drop in circulating noradrenaline and in arterial blood pressure and a significant linear correlation between the changes of plasma noradrenaline level and blood pressure was found after bromocryptine administration. There was no correlation between the rise in plasma beta ELI and the decrease in blood pressure after bromocryptine. The importance of the central sympathetic activity and not only a direct pituitary dopaminergic agonist effect on the beta-endorphin secretion can be stressed in the effect of bromocryptine on the immunoreactive beta-endorphin level.

The objective of the study was to investigate the efficacy of different dose levels of bopindolol monotherapy in hypertension. This potent nonselective beta-adrenergic receptor blocker has intrinsic sympathomimetic activity and long duration of action. Forty-four patients with essential hypertension of mild (n = 40) or moderate (n = 4) severity (90 less than DBP less than or equal to 115 mmHg at the end of the placebo period) entered and completed the single-blind, placebo-controlled trial. The study lasted 14 weeks: 2 weeks on placebo, and 12 weeks on active treatment during which the initial dose of bopindolol, 1 mg daily, was augmented up to 1.5 mg, then to 2 mg at four-week intervals until BP normalized or a maximum dose of 2 mg/day bopindolol was reached. The bopindolol was administered once a day in the morning. Patients were seen every other week in the morning before drug taking, when BP and heart rate, supine and standing, a twelve lead ECG and side-effects were recorded. Compared with placebo, supine BP was significantly reduced by bopindolol: from 169 +/- 2/103 +/- 1 mmHg to 148 +/- 3/92 +/- 1, 144 +/- 3/90 +/- 1 and 136 +/- 2/85 +/- 0.6 mmHg at the end of 4, 8 and 12 weeks of treatments, respectively (P less than 0.01 for each). BP changes during standing were similar. Bopindolol lowered the supine heart rate from 84 +/- 2 to 75 +/- 1, 74 +/- 1, 72 +/- 1 beats/min (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Prazosin (Minipress) monotherapy was given to 152 patients with essential hypertension for one year in a multi-center study involving 13 hospitals and university clinics. In three centers serum levels of total cholesterol, HDL-cholesterol and triglycerides were also determined in 32 patients with hypertension and hyper/dys-lipoproteinemia. As a consequence of Minipress monotherapy significant decreases were found in serum level of cholesterol (after three months and also after one year), triglycerides (after one year), while the serum concentration of HDL-cholesterol increased. Atherogenic index (a ratio of total cholesterol over HDL-cholesterol) was significantly decreased by Minipress. As new data showing a causative correlation between hypertension and hyperlipoproteinemia were published in the literature authors, on the basis of their results, suggest to determine lipid profile in every patient with hypertension. They regard Minipress as the first line drug in young patients with "familial dyslipidemic hypertension". When choosing an antihypertensive drug metabolic side effects should be taken into consideration.

The authors summarized the relationships between the cardiovascular diseases and smoking. In their retrospective study they studied the acute antihypertensive effect of nifedipine in patients with essential hypertension who were smokers and nonsmokers. They suggest that the antihypertensive effect of nifedipine did not decrease in smokers. Therefore the nifedipine can be the first choice in the antihypertensive therapy in smokers with essential hypertension.

The effect on systolic blood pressure and heart rate of the acute and chronic intraperitoneal (i.p.) administration of d- and dl-propranolol was investigated on unanesthetised spontaneously hypertensive rats. The effect of naloxone on the propranolol induced hypotension was also studied to test the hypothesis that the antihypertensive effect of propranolol involves the release of an endogenous opiate. On i.p. administration, 3 mg/kg d-propranolol was inactive; 3 and 30 mg/kg dl-propranolol decreased blood pressure and heart rate in a dose-dependent manner. When the rats were pretreated with 2 mg/kg naloxone i.p., the effect of propranolol on the blood pressure was nearly completely abolished, while that on the heart rate was only partially blocked. Chronic administration of dl-propranolol (30 mg/kg b.i.d.) to spontaneously hypertensive rats from the age of 6 weeks (prehypertensive phase) for 29 days prevented the development of hypertension while the rats treated with physiological saline for 29 days (control group) developed hypertension. Naloxone (2 mg/kg i.p.) administered on the 29th day to chronically treated rats induced a reversal of the propranolol action on systolic blood pressure and heart rate, i.e., blood pressure and heart rate increased. Naloxone had no such effect in the control group. We suggest that the release of an endogenous opioid contributes to the acute and chronic antihypertensive action of i.p. propranolol in spontaneously hypertensive rats and that the secretion of endogenous opioids participating in the control of cardiovascular functions is influenced by adrenergic mechanisms.

Renovascular disorders are rather rare in children and adolescents but have severe consequences due to complicating hypertension. Six cases successfully treated by surgery are described. The importance of early diagnosis and vascular correction is stressed; normalization of blood pressure has been achieved in every case.

Increased sensitivity to phenylephrin and a decreased one to isoproterenol has been found in regional vascular beds of GC implanted rats. Circulatory sympathetic reflex adaptation, alfa- and beta-adrenergic stimulation or blockade provoked a uniform response pattern: i.e. increase in vascular resistance of GC.

The effect of external compression on the postocclusion hyperaemic responses (occlusion time 15, 30, 60 sec) has been studied on the fibrillating canine heart. The heart was placed in a closed organ box containing physiological saline solution, and the coronaries were perfused with blood from a donor dog using a constant volume perfusion technique at 150 mmHg perfusion pressure. The pressure in the organ box varied between 0--50 mmHg. As the compression pressure increased in the organ box, coronary blood flow, basal conductance as well as the parameters of the postocclusion hyperaemic reaction (peak conductance, reactivity, mean transit time of hyperaemia, postocclusive conductance area, and repaymen) decreased. The factors (tissue diffusion, tissue pressure, transmural pressure) at the capillary level can influence the regulation of the postocclusion vasodilatation and the results cannot be explained by metabolic and/or myogenic processes alone.

Reactive hyperemia following occlusions of 15, 30, 60 and 120 sec duration was studied in the left coronary vascular bed of the isolated fibrillating dog heart perfused with arterial blood at constant pressure or constant volume. Except for repayment, linear correlations were found between occlusion time and the characteristics of reactive hyperemia. At a basal perfusion pressure of 50 mm Hg the postocclusion reaction was absent. The maximum hyperemic response was observed at 100 mm Hg, while on a further increase of perfusion pressure reactive hyperemia decreased. The postocclusion reaction was more marked but of briefer duration under constant pressure perfusion. The results can be explained by the joint effects of metabolic, myogenic, and physical factors on coronary vascular tone.

With a brief description of the physiological role of the renin-angiotensin-aldosterone system in the regulation of blood pressure the most important clinicopharmacological aspects of the converting enzyme inhibitor, captopril, is outlined. Hemodynamic and humoral effects, pharmacokinetics, indications, contraindications, dosage, side effects, drug interactions and usage in diagnostic procedures of captopril is described. The possibility of captopril therapy in children is also discussed.

48 patients with normal-renin essential hypertension were treated with prazosin alone or in combination with oxprenolol. 1 h after a single dose of 2 mg prazosin tachycardia and a decrease in blood pressure developed. Renin activity in the peripheral plasma (PRA) increased from 1.04 +/- 0.15 to 2.64 +/- 0.20 ng AgT/ml/h. A 3-day treatment with 2 mg t.i.d. prazosin of 11 patients caused no further decrease in blood pressure, while PRA returned to the baseline level. Treatment for 3 days with 2 mg prazosin t.i.d. and 40 mg oxprenolol t.i.d. of 37 patients further decreased blood pressure as well as PRA. The increase in PRA after a single dose of prazosin could be related to the enhanced sympathetic activity. The decreased PRA after prazosin + oxprenolol therapy may be one of the factors responsible for the greater antihypertensive response to the combined therapy.

The medical history of 256 hypertensive and 263 normotensive pregnant women was analysed retrospectively. There was a negative correlation (P less than 0.01) between the maximal pretreatment diastolic blood pressure and the birth weight of newborns in the hypertensive group. The prevalence of a hypertensive family history, pyelonephritis, proteinuria, delivery by Caesarean section, fetal asphyxia during delivery and death of the newborn during delivery was significantly higher in the hypertensive group than in the normotensive one. The gestational age at delivery was shorter and the birth weight of the newborn was lower in the hypertensive women than in the normotensive women.

Effects of phenoxybenzamine (1 mg per 100 g i.v.), propranolol (0.2 mg per 100 g i.v.), phenylephrine (0.1--0.3--1.0--3.0 micrograms per 100 g per min) and isoproterenol (0.01--0.03--0.1--0.3 micrograms per 100 g per min) were studied on cardiac output (Evans-blue dilution), organ and tumour blood flows (Sapirstein's isotope indicator dilution technique) in rats bearing Guérin carcinoma. In agreement with our earlier results data for haematocrit, blood pressure, TPR and organ vascular resistance were lower whereas cardiac index and organ blood flow were higher in control untreated tumour-bearing animals than in untreated normal rats. Phenoxybenzamine, depending on tumour size, decreased blood pressure, TPR and vascular resistance of organs, while it was found ineffective in rats with tumours of very large size (60--80 g). Propranolol treatment produced slight and similar effects in both normal and tumour-bearing rats. Phenylephrine enhanced peripheral resistance as a function of log dose in both normal and tumour bearing animals, nevertheless in the latter group it elicited more marked responses in the vascular bed of the kidneys, intestines and skin. The vasodilatory log dose dependent effect of isoproterenol was not present in tumour-bearing rats. In addition to the anaemia, the continuous decrease of alpha adrenergic activity in the systemic circulation parallel with tumour growth appears to be the most reasonable explanation for the "hyperkinesis" observed in tumour-bearing rats. Resistance of tumour vascular bed was increased by both phenoxybenzamine and propranolol. During the course of phenylephrine infusion (1.0 or 3.0 micrograms per min) the resistance of tumour vessels was more increased than that of other organs. Isoproterenol infusion resulted in a vasoconstriction of the tumour vessel. It appears that with maximally dilated vessels, vasoconstriction remains the only possible vascular response in Guérin carcinoma. In the vascular bed of the tumour a preponderance of beta adrenergic receptors also seems to be feasible.

Diurnal rhythm of plasma beta endorphin was established with the highest level in the morning and the lowest one at midnight in normotensive subjects and also in patients with essential hypertension. Clonidine (300 micrograms daily) significantly increased plasma beta endorphin concentrations only in the hypertensive patients. The significant linear correlation between the increase in plasma beta endorphin concentration and the decrease in blood pressure (both systolic and diastolic) in these patients may point to the role of this endogenous opioid in the antihypertensive action of clonidine.

Cardiac output (CO), blood pressure (BP) and heart rate (HR) were estimated in 13 non-athletes, in 10 highly trained athletes and in 8 lower-class athletes at rest. HR and BP were found to be lower in both trained groups than in the controls. CO was lower in the top athletes, while it proved to be higher in the lower-class athletes. Total peripheral resistance (TPR) was higher in the top athletes while it was found to be reduced in the lower-class athletes than in the controls. These results indicate that in the maintanance of resting blood pressure level in the physically trained subjects alpha adrenergic mechanisms predominate whereas the share of beta influences is lower, however, this shift is observed only in the highly trained, top-rank endurance athletes.

In various forms of shock, TRH is equivalent to naloxone in reversing the hypotension and improving the survival rate. The present findings indicate that in spontaneously hypertensive rats (SHR), TRH has another naloxone-like effect in antagonizing the antihypertensive response to clonidine and alpha-methyldopa. When given during the hypotensive response to alpha-methyldopa, both naloxone and TRH produce a pressor response. While this effect of naloxone is blocked by prazosin, the effect of TRH is not influenced by prazosin or hexamethonium but is inhibited by a vasopressin pressor antagonist. This suggests that the pressor response to naloxone is mediated by the sympathetic nervous system, whereas the similar action of TRH is independent of sympatho-adrenomedullary functions and it is mediated by vasopressin.

In an acute, double-blind, crossover study on 12 patients with essential hypertension, the interaction between nifedipine and prazosin was investigated in the supine position. The effectiveness of the combination of the two active drugs was greater than the combination of either of the drugs plus placebo. The effect of nifedipine was not modified by prazosin pretreatment; however, the effect of prazosin was partly inhibited, i.e., delayed, by nifedipine pretreatment. Therefore, giving prazosin as a first drug and nifedipine as the second drug seems to be a better approach than the reverse.