Antihypertensive effect of amlodipine compared with nifedipine retard in patients with mild and moderate essential hypertension

OBJECTIVE: The present study was undertaken to evaluate the efficacy and safety of amlodipine for hypertension treatment in comparison with nifedipine retard. METHODS: We examined 31 patients with arterial blood pressure approximately 155-165 mmHg/100-105 mm Hg at the beginning of the trial. It was a randomized double-blind, parallel-group trial including two groups of patients. Patients of the first group were given active amlodipine and nifedipine retard placebo during 6 weeks, while the second group was given active nifedipine retard and amlodipine placebo. Statistical analysis was made using the paired Student's t-test, chi-square test and ANOVA test. RESULTS: At end point we observed significant decrease in arterial blood pressure after treatment of both drugs. The treatment with nifedipine retard increased the mean heart rate of patients. Amlodipine therapy in comparison to nifedipine retard did not change the heart rate in treated patients. Safety parameters: SGOT, SGTP, creatinine and others were in laboratory norms ranges. CONCLUSION: Amlodipine proved to be an effective, more safe and better-tolerated therapeutical alternative for hypertension management than nifedipine retard.     

The effect of minoxidil on blood pressure and plasma renin activity in patients with essential and renal hypertension

The effect of the new vasodilator, minoxidil, on blood pressure and plasma renin activity was studied in 21 hypertensive patients: 12 patients with essential and 9 with renal hypertension. The average maximum dosage of minoxidil was 27.9 +/- 6.0 mg/day (M +/- SD). Average duration of treatment was 84.5 days. During the observation period the average systolic blood pressure fell from 195 +/- 18 to 159 +/- 7 mm Hg (M +/- SD), and the mean diastolic blood pressure fell from 120 +/- 8.3 to 92.5 +/- 8 mm Hg (p less than 0.01). These patients had been treated earlier with other antihypertensive agents, such as reserpine, saluretics, hydralazine, alpha-methyldopa, and clonidine, without any significant reduction in blood pressure. Before treatment, plasma renin activity after resting was 59 +/- 6.4 ng/ml/16 h (M +/- SE) and after saluretics and orthostasis 89 +/- 12.7 ng/ml/16 h. After treatment, the decline in renin value after resting was statistically significant: 42.7 +/- 3.3 ng/ml/16 h (p less than 0.05), and the stimulated renin had fallen to 70 +/- 3.4 ng/ml/16 h (p greater than 0.1). A comparison of the renin stimulation values of patients with renal hypertension also revealed a significant reduction (p less than 0.01). Side effects which appeared at a daily dose of 15 to 30 mg consisted mainly of tachycardia and fluid retention and could be controlled by the administration of propranolol and chlorthalidone. In 5 women and in 1 man was observed a cosmetically disturbing, reversible hypertrichosis. Orthostatic hypotension was observed in one patient. Minoxidil is an effective antihypertensive agent. However, because of its side effects, it generally must be administered with beta-receptor blocking agents and saluretics. It is possible that its blood pressure lowering effect is due, at least in part, to a suppression of the plasma renin activity.     

Moxonidine effect on microalbuminuria, thrombomodulin, and plasminogen activator inhibitor-1 levels in patients with essential hypertension

The authors report a case of internal carotid artery dissection in a young woman with Beh?et's syndrome. The authors postulate that a vasculitis of the vasa vasorum already suspected as the basis of aneurysm formation in course of Beh?et's syndrome can account for occurrence of arterial dissection in this inflammatory condition.     

Anti-oxidant status and lipid peroxidation in patients with essential hypertension

BACKGROUND: Lipid peroxidation and derived oxidized products are being intensively investigated, because of their potential to cause injury and their pathogenetic role in several clinically significant diseases. The view that an excess of lipid peroxidation products is present and relevant in the pathogenesis of human essential hypertension or in hypertension-induced damage has still not received definitive support. OBJECTIVE: To evaluate both the extent of lipoperoxidation in essential hypertensive patients and the status of enzymatic and non-enzymatic antioxidants that potentially are able to modulate it METHODS: We selected 105 newly diagnosed essential hypertensives among those referred to our hypertension outpatient clinic and compared them with 100 normotensive controls matched for age. Plasma malondialdehyde was measured by high-performance liquid chromatography after reaction with thiobarbituric acid, as an end product of lipid peroxidation; serum selenium (Se), plasma copper (Cu) and zinc (Zn), vitamins A and E, erythrocyte superoxide dismutase and glutathione peroxidase levels were evaluated as indices of oxidant balance. Differences between the groups were tested by Student's t test and chi2 test. RESULTS: Compared with controls, essential hypertension patients had higher malondialdehyde and glutathione peroxidase activities (P<0.05 for both) and Zn concentrations (P<0.001) and lower superoxide dismutase activities (P<0.005), vitamin A (P<0.05) and E (P<0.001) levels and Cu concentrations (P<0.005). We found no difference between Se levels of essential hypertensive and control subjects. CONCLUSIONS: Essential hypertension is associated with greater than normal lipoperoxidation and an imbalance in anti-oxidant status, suggesting that oxidative stress is important in the pathogenesis of essential hypertension or in arterial damage related to essential hypertension.     

Renal depressor mechanisms of physical training in patients with essential hypertension

To clarify characteristics of the patients in whom exercise training lowers blood pressure and to elucidate the mechanisms by which exercise training lowers blood pressure, we evaluated 24-h blood pressure, glomerular filtration rate (GFR), renal blood flow (RBF), filtration fraction (FF), plasma renin activity (PRA), plasma aldosterone concentration (PAC), plasma norepinephrine concentration (PNE), and incremental area of insulin/glucose (sigmaI/sigmaG) during 75 g oral glucose tolerance test, and assessed arterial baroreceptor function (BSI) before and after a 3-week exercise training program (four 6-min sessions daily at 75% VO2 max). Patients were classified as responders (n = 15) if they showed statistically significant reduction in the multiple comparison of 24-h mean arterial pressure (MAP), or as nonresponders (n = 15) if they did not. Although there were no significant differences between responders and nonresponders in age, weight, MAP, GFR, RBF, RPF, FF, PNE, sigmaI/sigmaG, or BSI before exercise, renal vascular resistance (RVR; P < .05), PRA (P < .05), and PAC (P < .05) were significantly higher in responders than in nonresponders. The fractional excretion of sodium (FENa) (P < .05) were significantly lower in responders than in nonresponders. After exercise training, FF (P < .01), RVR (P < .05), PNE (P < .05) PRA (P < .01), and sigmaI/sigmaG (P < .05) decreased significantly only in responders. The decrease in MAP significantly correlated with the reductions in FF (r = 0.46, P < .05), PNE (r = 0.52, P < .01) and RVR (r = 0.40, P < .05). Thus, in patients who have higher RVR and PRA, exercise training lowered blood pressure in parallel to a reduction in RVR associated with decreases in sympathetic tone and improvement of insulin resistance. Our results suggest that exercise-induced changes in renal hemodynamics may contribute to the reduction in blood pressure in these patients.     

Histology of subcutaneous small arteries from patients with essential hypertension

The purpose of the present study was to determine the cellular basis for the increased ratio of media thickness to lumen diameter (media-lumen ratio) consistently found in the peripheral resistance arteries from patients with essential hypertension using an unbiased stereological principle (the "disector"). Segments of subcutaneous resistance arteries (approximately 200 microns internal diameter) were isolated from gluteal biopsies of skin and subcutaneous fat taken from 16 untreated patients with essential hypertension and 16 age- and sex-matched normotensive control subjects. Measured under standardized conditions (ie, relaxed and under controlled mechanical conditions) on an isometric myograph, vessels from hypertensive patients had a significant (P < .05) reduction in lumen diameter and an increase in media-lumen ratio (P < .05) compared with vessels from normotensive control subjects. These changes were not associated with alterations in the estimated media volume per segment length. After these measurements had been made, the arteries were fixed, serial sectioned, and stained. The volume fraction of smooth muscle cells within the media was estimated by point counting on photomicrographs of the vessels. Using the disector principle, we determined the numerical density (number per unit volume) of smooth muscle cells within the media of each vessel and calculated the average smooth muscle cell volume (1775 +/- 122 [mean +/- SEM] and 1532 +/- 112 microns 3, hypertensive and normotensive, respectively, P > .05) on the basis of these measurements.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of L-arginine on systemic and renal haemodynamics in salt-sensitive patients with essential hypertension

In response to a high sodium (Na+) intake, salt-sensitive patients with hypertension retain more Na+ and manifest a greater rise in arterial pressure than salt-resistant patients. Because there is limited information regarding the role of nitric oxide (NO) in salt-sensitivity we examined the effects of L-arginine (500 mg/kg, i.v. for 30 min) on mean arterial pressure and renal haemodynamics in 21 hypertensive and five normotensive African-Americans. At the end of L-arginine infusion mean arterial pressure fell more in salt-sensitive (-11.5 +/- 2.5) than in salt-resistant (-3.7 +/- 1.5 mm Hg) and control subjects (-3.2 +/- 3.8 mm Hg). At the end of L-arginine infusion effective renal plasma flow (ERPF) increased more (P < 0.05) in controls (+108 +/- 13.9 ml/min/1.73 m2) than in salt-resistant (+55 +/- 16.0 ml/min/1.73 m2) and salt-sensitive patients (+22 +/- 21.5 ml/min/1.73 m2). This study has shown that salt-sensitive African-Americans manifest different systemic and renal haemodynamic responses to L-arginine than salt-resistant patients and controls. The fall in mean blood pressure following L-arginine was greater in salt-sensitive than in salt-resistant patients and controls, whereas the increase in ERPF was reduced in salt-sensitive compared to salt-resistant and normal subjects. The data are in keeping with the notion that a defect in NO production may participate to the genesis of blood pressure sensitivity to salt.     

Influence of risk factors and pharmacological treatment on mortality in patients with essential hypertension

BACKGROUND: The V JNC consensus stated that although new antihypertensive agents, such as angiotensin converting enzyme inhibitors and calcium channel blockers, are considered safer drugs, there is no firm evidence from large controlled trials that these drugs are associated with a lower cardiovascular mortality. AIM: To study the association between cardiovascular risk factors, blood pressure levels, pharmacological treatment and mortality in a group of hypertensive patients followed at an hypertension outpatient clinic. PATIENTS AND METHODS: Patients with essential hypertension were treated with different antihypertensive medications, according to physicians criteria, and controlled until death or loss from follow up. Causes of death were obtained from hospital records and death certificates. Survival was analyzed using life tables, comparisons between groups of patients were done using chi square or a Cox's proportional hazards model. RESULTS: Three hundred thirty-nine hypertensive patients aged 33 to 80 years old were followed for a mean period of 9.8 +/- 4.9 years. Eighty-six were treated with beta blockers, 64 with diuretics, 133 with calcium antagonists and 56 with ACE inhibitors. Blood pressure dropped similarly with all medications. During follow up, 79 patients died. Life table analysis showed that patients with a history of angina, diabetes or myocardial infarction had higher mortality rates. Similarly, patients treated with beta blockers and diuretics had higher mortality than patients treated with calcium antagonists or angiotensin converting enzyme inhibitors. The proportional hazards model showed that the effect of treatment modality persisted after correction for the other risk factors for mortality. CONCLUSIONS: In this series of hypertensive patients, those treated with beta blockers or diuretics had higher mortality rates than those receiving calcium channel antagonists or angiotensin converting enzyme inhibitors.     

Beneficial effect of the ACE inhibitor captopril in normotensive patients with insulin-dependent diabetes

The increase of glomerular filtration can often be observed in patients with insulin dependent diabetes mellitus, even in the early stage of the disease and it does not require the presence of microalbuminuria. This phenomenon can be explained by vasoconstriction occurring in the efferent arterioles. Eighteen normotensive, diabetic patients (aged: 28-42) who developed increased glomerular filtration were recruited in this study. The specific objectives were: 1. to study the beneficial effect of angiotensin converting enzyme inhibitor on the glomerular filtration, 2. to evaluate the effect of this treatment on blood pressure and hemodynamic parameters in normotensive, diabetic subjects. After a placebo period of one week, patients were treated orally a daily dose of 3 x 6.25 mg of captopril for twelve weeks. Glomerular filtration was assessed by the isotopic clearance method and blood pressure recordings were taken every 30 minutes throughout a day using an automatic programmable device. Preload, afterload and linear ejection fraction were estimated by echocardiograph, whereas cardiac index was measured by isotopic first pass technique. At the end of the treatment period a significant decrease of glomerular filtration was observed (from 141.9 +/- 10 ml/min to 98.9 +/- 12 ml/min; p < 0.01. Similarly, the afterload exhibited a significant drop due to drug treatment (45.6 +/- 5.8 x 10(3) dyn/cm2 vs. 55.4 +/- 4.7 x 10(3) dyn/cm2 at the end of the placebo period (p < 0.01). However, preload, linear ejection fraction, and cardiac index did not significantly change during the treatment. According to the results obtained from this study a beneficial effect of captopril on the early development of the glomerular hyperfiltration was demonstrated in normotensive diabetic patients who did not develop microalbuminuria. This issue needs to be investigated further in a large scale clinical trial.     

Effect of oral pyridoxine hydrochloride supplementation on arterial blood pressure in patients with essential hypertension

The purpose of this study was to test the effect of vitamin B6 (pyridoxine-HCl, CAS 58-56-0) supplementation on arterial blood pressure in essential hypertension. The trial comprised 9 normotensive subjects (7 men and 2 women, aged between 32-58 years; mean +/- SD, 48 +/- 11) and 20 patients with essential hypertension (16 men and 4 women, aged between 32-69 years; mean +/- SD, 56 +/- 12). The patients were treated during 4 weeks with a single oral dose of pyridoxine (5 mg/kg body weight/day). After a 5-min rest, measurements were made in the supine position. When compared with the normotensive subjects, the hypertensive subject group had a significantly higher systolic and diastolic blood pressure (p < 0.001) and higher level of plasma norepinephrine (NE) (p < 0.01) before pyridoxine treatment. On the other hand, there were no significant differences in plasma epinephrine (E) and heart rates. Treatment of hypertensive patients with pyridoxine significantly reduced systolic (p < 0.01) and diastolic blood pressure (p < 0.005), plasma NE (p < 0.005) and E (p < 0.05) within 4 weeks. However, there was no significant difference in heart rate at the end of pyridoxine treatment. These results indicate a relationship between pyridoxine status and arterial blood pressure in the essential hypertensive patients.     

Serum angiotensin converting enzyme activity in patients with untreated essential arterial hypertension

The serum angiotensin converting enzyme (ACE) in 30 patients with untreated essential arterial hypertension, 30 patients with chronic renal failure accompanied with arterial hypertension and 30 healthy individuals was measured. The subjects of both sexes have been old 35-60 years. The serum ACE activity was determined by the spectrophotometric method, using Hip-Gly-Gly as a substrate. The serum ACE activity significantly increased in patients with arterial hypertension (32.48 +/- 2.02; X +/- SEM) and patients with chronical renal failure accompanied with arterial hypertension (37.10 +/- 1.45) when compared to the healthy individuals (20.83 +/- 1.33). Possible mechanisms of increasing ACE activity with the patients suffering of arterial hypertension are discussed.     

Influence of aging on progression of cardiovascular complications associated with insulin resistance in patients with essential hypertension

A simplified method of diagnosing anterior divisional blocks (hemiblocks) at a glance is made possible by using a knowledge of the lead line directions on a hexaxial system. The term 'divisional block' is preferred to 'hemiblock' because a block of one of the three divisions of the left bundle cannot be a hemiblock. The diagnosis of an anterior divisional block can be simplified by utilization of the concept that it is mainly a terminal conduction abnormality in the frontal plane with a direction between -60 degree and -90 degree. Using a hexaxial system the diagnosis can be quickly made regardless of axis by simply noting the presence of a terminal negativity (S wave) in aVF, terminal positivity in aVR (R or R'), and no S in lead 1.     

Inhibition of plasma endothelin-1 concentration by captopril in patients with essential hypertension

The aim of this study was to determine whether captopril has any effect on plasma endothelin-1 (ET-1) concentration in patients with essential hypertension. Nine normotensives and eleven hypertensives were included in this study. Blood pressure and pulse rate were monitored before and at 60 min after captopril ingestion (25 mg). Simultaneously, blood samples for plasma ET-1 and plasma renin activity (PRA) determination were obtained. In the normotensives, captopril treatment resulted in a significant rise in PRA, but without statistical changes in blood pressure and plasma ET-1. By contrast, in the hypertensives, although PRA elevated similarly after captopril, both blood pressure and plasma ET-1 decreased significantly compared with their respective preloading level. These data suggest that the blood pressure-lowering effect of captopril in essential hypertension may be at least in part, mediated by its inhibition of ET-1 production from the vascular endothelium.     

Parallel comparative trial of amlodipine and nitrendipine monotherapy in patients with essential hypertension

OBJECTIVES: To compare the blood pressure effects of two dihydropyridine calcium channel blockers, amlodipine and nitrendipine, in 488 patients with essential hypertension. METHODS: The study used a randomized, single-blind design of 4 weeks' duration conducted at four medical centres in China. Patients were randomized to receive either amlodipine monotherapy (5-10 mg once daily; n = 334) or nitrendipine (10 mg twice or three times daily; n = 1 54). Blood pressure was evaluated by standard blood pressure measurements before and after treatment, and by 24 h ambulatory blood pressure monitoring in a subgroup of patients (n = 18). RESULTS: Both systolic and diastolic blood pressures were reduced from baseline after 4 weeks of amlodipine and nitrendipine monotherapy. Diastolic blood pressure was reduced by 14.4% in the amlodipine group, which was significantly better than the 13.0% reduction in the nitrendipine group (P< 0.05). In addition, blood pressure response rates were significantly better with amlodipine monotherapy than with nitrendipine monotherapy. In the subgroup of patients undergoing 24 h ambulatory blood pressure monitoring, both systolic and diastolic blood pressure were reduced from baseline in the amlodipine and nitrendipine groups. Adverse effects were generally mild, with dizziness, flushing, palpitation, headache, drowsiness and ankle oedema being the most common. Rushing and headache were more frequent in the nitrendipine group than in the amlodipine group (P< 0.05 for flushing and P<0.01 for headache). CONCLUSIONS: Amlodipine monotherapy reduced blood pressure more effectively than nitrendipine monotherapy in patients with essential hypertension and was associated with fewer adverse events.     

Changes in the intracardiac hemodynamics of patients with essential hypertension during korinfar treatment

A study is presented of the structure and function of the heart in the diastole in 39 patients during corinfar treatment of essential hypertension. It was established that effective corinfar monotherapy of patients with moderate essential hypertension was associated with arteriolo- and venodilating effect of the drug with prevalence of the preloading effect. Changes of the intracardiac hemodynamics resulted in changes of the left ventricular systole phase structure, namely, its transformation in the direction of myocardial hypodynamia.     

Carotid intima-media thickening and in vivo LDL oxidation in patients with essential hypertension

Low density lipoproteins (LDL) from hypertensive patients are more prone to in vitro oxidation and undergo a more pronounced oxidation in vivo. Due to the pro-atherogenic activity of oxidatively modified LDL, the correlation between the carotid intima-media thickening (IMT) and the markers of in vivo LDL oxidation was investigated in hypertensive patients. A cross-sectional study on 101 normocholesterolemic patients with newly diagnosed and untreated essential hypertension was performed. The occurrence of in vivo LDL oxidation was evaluated by measuring the titers of autoantibodies against Cu(2+)-oxidised LDL (oxLDL) and malondialdehyde-derivatised LDL (MDA-LDL). The extent and degree of atherosclerosis and the IMT were measured by means of carotid and femoral ultrasonography with a duplex scanner equipped with a high resolution probe. We did not find significant correlations between in vivo LDL oxidation parameters and the extent of atherosclerotic lesion in the entire group of hypertensive patients. However, a significant direct correlation was detected between the carotid IMT and the titer of autoantibodies against both oxLDL and MDA-LDL in hypertensive patients without advanced atherosclerotic plaques. The results obtained support the hypothesis that enhanced LDL oxidation may be one of the pathophysiological events related to the formation and progression of early atherosclerotic lesions (IMT) in carotid arteries of hypertensive patients.     

The treatment of patients with benign prostatic hyperplasia using the selective alpha-blocker alfuzosin

40 patients with benign prostatic hyperplasia (BPH) were treated with the alpha-blocker alfuzosin which was administered per os twice a day in a dose 5 mg. The treatment brought about a decrease of the mean symptom score from 19.6 to 12.2, of quality of life from 5.2 to 2.1, of residual urine from 152 to 82 ml. Mean and maximal urinary flow rates rose by 35 and 45%, respectively. The level of prostate-specific antigen over the treatment course did not change. The findings of the trial evidence for high efficacy of alfuzosin in the treatment of urination disorders in BPH patients.