Antihypertensive and cardiovascular effects of nitrendipine: a controlled study vs. placebo.

The antihypertensive and cardiovascular effects of nitrendipine, a calcium entry blocker similar to nifedipine, have been evaluated in a double-blind, placebo-controlled study in 20 patients with hypertension. At baseline and at the end of the 8-week period (nitrendipine, 20 mg once a day, or placebo, 1 tablet once a day) the following parameters were measured: systolic and diastolic blood pressure (BP) and heart rate (HR) at rest by an automatic recorder; BP, HR, and cardiac workload (systolic BP X HR) during exercise testing on a bicycle; left ventricular mass (LVMe according to the method of Devereux) and cross-sectional area (CSA), and main parameters of systolic function (end diastolic volume, end systolic volume [ESV], and ejection fraction [EF]) by M mode echocardiography. There was a significant decrease in BP at rest (163/108 vs. 144/92 mm Hg; P less than 0.001) and during exercise in subjects receiving nitrendipine, while placebo did not modify these parameters. LVMe (from 195 to 188 gm; P less than 0.01) and CSA (from 20.2 to 19.8 cm2; P less than 0.05) were reduced by nitrendipine, which also improved cardiac performance (ESV fell from 44 to 38 ml [P less than 0.001] and EF fell from 62% to 66% [P less than 0.01]). No effect was observed in the placebo group. Our results indicate that nitrendipine is a powerful antihypertensive agent that also improves cardiac performance and slightly but significantly reduces left ventricular mass.

Cardiovascular effects of ketanserin, a new antiserotonergic agent in the treatment of arterial hypertension.

Ketanserin, an investigational, antiserotonergic agent, at a dose of 40 mg bid was given to 18 patients with mild to moderate primary hypertension in a randomized, double-blind, crossover study, with 100-mg metoprolol bid for four weeks each. The following parameters were evaluated: blood pressure, heart rate, cardiac workload (product of systolic blood pressure and heart rate during bicycle exercise), systolic time intervals, and peripheral blood flow (by strain-gauge plethysmography). Significant reductions in diastolic and concomitant slight decreases in systolic blood pressure without changes in heart rate were observed during ketanserin treatment; cardiac oxygen demands during exercise test did not change, however. Pre-ejection period and left ventricular ejection time were unchanged, while significant increase in rest flow to the lower limbs and decrease in peripheral resistance were demonstrated by strain-gauge plethysmography. The results indicate that ketanserin has vasodilating properties and hypotensive activity that may be useful in the management of patients with essential hypertension.

Obesity and beta-blockers: influence of body fat on their kinetics and cardiovascular effects.

Beta-blockers are among the most widely used antihypertensive drugs. They differ from each other in regard to several factors such as: beta-agonist activity, beta 1-selectivity and solubility. Aim of this work was to evaluate the influence of obesity on the kinetics and the antihypertensive effect of two Beta-blockers with different solubility such as: the water-soluble, atenolol and the liposoluble, metoprolol. The study was carried out according to an open randomized cross-over design. Eight obese hypertensive patients, after a two week washout period, were randomly allocated to a four week treatment. After a two week intermediate washout period, each patient switched to the other treatment for an additional four week period. On the first and the last day of each treatment the subjects were hospitalized to collect blood samples for the assay of the two drugs and to measure cardiovascular parameters. Obesity does not exert any effect on the kinetics of the water-soluble beta-blocker, atenolol, while markedly interferes with that of the liposoluble, without any apparent influence on its anti-hypertensive effect. These findings extend to obese hypertensives the concept that the plasma concentrations of beta-blocking agents are not reliable predictors of their therapeutic effect.

Long-term antihypertensive efficacy of ketanserin plus chlorthalidone.

The long-term antihypertensive efficacy of a combination of ketanserin (20 mg), an S2 antagonist with alpha 1 blocking activity, and chlorthalidone (25 mg), given o.d., was evaluated in fifteen patients with primary hypertension of mild to moderate degree, aged 45-65 years, up to a 12-month observation period. Systolic (SBP) and diastolic (DBP) blood pressure, and heart rate (HR) were measured by an automatic recorder (Sentron Bard Biomedical) twice at rest after 5 min in a supine position and after 2 and 5 min in an upright position, 24 h after the last antihypertensive dose. Thirteen patients completed the study whilst two were lost to the follow-up. A significant reduction was observed in both SBP and DBP at rest. In particular, SBP was reduced from 167 +/- 17 mmHg to 152 +/- 21 mmHg (p less than 0.01) after 1 month of therapy and was kept constant at this level throughout the observation period. DBP was also reduced from the first control [99 +/- 7 vs. 90 +/- 9 mmHg (p less than 0.01)] without any increase during the follow-up. HR was unchanged throughout the study. Four patients had dizziness and orthostatic hypotension after the first dose of the drug combination but were able to continue the study without further adverse reactions. These data support the conclusion that long-term treatment with the combination of a small dose of ketanserin and chlorthalidone is able to reduce systolic and diastolic blood pressure, without remarkable untoward side-effects.

Haemodynamic changes in peripheral arterial circulation during antihypertensive treatment with captopril, methyldopa and indapamide.

Structural changes in resistance vessels of the lower limbs have been detected in early stages of arterial hypertension. In these patients it might be important to reduce blood pressure by drugs which do not impair peripheral blood flow. Twenty-four patients with arterial hypertension, without target organ damage were randomly given a placebo, 50 mg captopril, 500 mg methyldopa or 2.5 mg indapamide and their blood pressure, arterial blood flow and peripheral resistance were measured at baseline and at the peak action of the antihypertensive treatment. Significant decreases in blood pressure and peripheral resistance have been induced by a single oral dose of captopril and methyldopa: a concomitant significant increase in peripheral blood flow to the lower limbs was also observed during methyldopa treatment. No acute effect was observed on the placebo or on indapamide: the latter induced a decrease in blood pressure and in peripheral resistance along with an increase in arterial blood flow during long-term treatment after four weeks of therapy. Our observations seem to support the usefulness in hypertensive patients with concomitant lesions in the peripheral arterial tree of antihypertensive agents such as methyldopa and indapamide which increase blood flow and reduce peripheral resistance while lowering high blood pressure.

Blood pressure during a combination of ketanserin and hydrochlorothiazide.

The antihypertensive effectiveness of a combination of ketanserin 20 mg plus hydrochlorothiazide 25 mg has been evaluated in 20 patients with arterial hypertension of mild to moderate degree in the age group over 50 years (age range 50-78 years). After a wash-out period of at least two weeks, patients were given a single oral dose of ketanserin 20 mg or thiazide 25 mg in a randomized order at two-day intervals and blood pressure, heart rate and cardiac workload (systolic blood pressure x heart rate) were measured during the following 24 h by an automatic recorder. Thereafter patients were given the combination of the two drugs for six weeks and 24 h blood pressure was assessed after the first dose and at the end of the treatment. A significant fall in systolic and diastolic blood pressure was rapidly induced by ketanserin from 2 to 8 h after dosing; thiazide on the other hand did not induce any change in these parameters (169 +/- 15/95 +/- 6 mmHg (22.5 +/- 2.0/12.7 +/- 0.8 kPa) at baseline versus 153 +/- 17/89 +/- 7 mmHg (20.4 +/- 2.3/11.9 +/- 0.9 kPa) at 2 h and 157 +/- 19/87 +/- 8 mmHg (20.9 +/- 2.5/11.6 +/- 1.1 kPa) at 8 h on ketanserin; 166 +/- 15/93 +/- 6 mmHg (22.1 +/- 2.0/12.4 +/- 0.8 kPa) at baseline versus 160 +/- 12/89 +/- 6 mmHg (21.3 +/- 1.6/11.9 +/- 0.8 kPa) at 2 h and 157 +/- 15/89 +/- 5 mmHg (20.9 +/- 2.0/11.9 +/- 0.7 kPa) at 8 h on thiazide).(ABSTRACT TRUNCATED AT 250 WORDS)

Pain threshold in humans. A study with the pressure algometer.

Pain perception threshold (PPT) in the head was assessed with a pressure algometer in 40 control individuals (24 females and 16 males). Threshold was assessed at 11 symmetrical points on each side. The average threshold for each side was calculated, and differences between two sides were evaluated with an asymmetry index. Subjects were studied in relation to age and sex, and any difference in the symmetrical perception of pain on the head was registered. The deltoid muscle was chosen as a reference point, since it is rarely a site of trigger points. The reproducibility of the method was satisfactory. A significantly positive correlation was found between PPT value of the head and the deltoid muscle. There was no tendency to rise or fall in PPT during the same "session", which consisted of 3 separate complete measurements. The mean of mean values showed that there was little asymmetry as for the thresholds pertaining to the head in the total material. Age and sex apparently played little role as for the outcome of the test. The assessment of PPT in the head might be a useful tool in the study of lateralization of pain in unilateral headache syndromes.

Double-outlet right ventricle with intact ventricular septum.

In the present case report, we describe a malformation consisting of a double-outlet right ventricle with an intact ventricular septum diagnosed in a 3-day-old female newborn. To our knowledge 35 cases have been described in the literature. The diagnosis was made by two-dimensional echocardiography and confirmed by angiocardiography. An inadequate opening in the interatrial septum and hypoplasia of the mitral valve and left ventricle were present. In this condition the only outlet of the left ventricle is via the atrial septal defect. Balloon atrial septostomy was performed. At 1 month of age the patient required a right modified Blalock-Taussig shunt and surgical atrial septectomy. Five months after surgery, the patient was in good clinical conditions.

[Dilated thyrotoxic cardiomyopathy]. / Cardiomiopatia dilatativa tireotossica.

We report a case of reversible, dilated cardiomyopathy due to thyrotoxicosis, which occurred in a young male without any underlying heart disease. The patient presented a clinical picture of cardiogenic shock related to severe left ventricular dilation and dysfunction and with new-onset atrial fibrillation and very high ventricular rate. In spite of vigorous medical therapy, there was only a mild improvement of clinical and hemodynamic status and ventricular rate persisted inappropriately elevated. Subsequently, laboratory test results allowed for recognition of thyrotoxicosis (secondary to Graves's disease) and then specific thyrostatic treatment was added. There was a prompt clinical improvement and parallel, progressive reversal of left ventricular dysfunction. The patient could be converted to normal sinus rhythm and one week later was discharged in good condition. We discuss the pathophysiological mechanism for the induction of this rare form of thyrotoxic cardiomyopathy and emphasize that awareness of this possible presentation of hyperthyroidism is essential to identify patients with potentially reversible dilated cardiomyopathy.

Age related antihypertensive effect of nitrendipine, a new calcium entry blocking agent.

The effect of nitrendipine 20 mg o.d., a new calcium entry blocker similar in structure to nifedipine, on blood pressure has been evaluated in 14 patients (aged 24-62 years) with uncomplicated mild or moderate arterial hypertension. A significant decrease both in systolic (160 +/- 12 at baseline vs 141 +/- 8 mm Hg, p less than 0.001) and diastolic (106 +/- 8 vs 93 +/- 3 mm Hg, p less than 0.001) blood pressure was observed at the end of 8 weeks of nitrendipine treatment. An inverse correlation was found between age and the reduction in diastolic blood pressure (r = 0.772, p less than 0.001 as absolute reduction; r = 0.791, p less than 0.001 as percentage reduction versus baseline). This peculiar characteristic differentiates the effect of nitrendipine from that of other calcium entry blockers, which appear to be more effective in older patients.

Study with the competitive 5-HT2-serotonergic antagonist ketanserin.

In 10 patients with primary arterial hypertension of mild or moderate degree, ketanserin, a competitive antagonist of serotonin receptors, was given for a period of 4 weeks, 40 mg twice daily. In a control group, patients were given 100 mg twice daily of metoprolol for 4 weeks for each treatment. A randomized double-blind crossover model was used. Blood pressure and heart rate were measured at rest and during exercise testing on a bicycle; peripheral blood flow was measured by strain-gauge plethysmography. A slight reduction in resting systolic and diastolic blood pressure without change in heart rate was observed during treatment with ketanserin. Cardiac workload during exercise test did not change over the observation period. A slight increase in resting blood flow to the lower limbs, with a decrease in peripheral resistance was demonstrated by strain-gauge plethysmography.

Effects of ketanserin on intraocular pressure.

There is evidence that some antihypertensive drugs, such as beta blockers, are effective in reducing intraocular pressure (IOP) and are commonly used in the medical treatment of glaucoma. The aim of this study was to evaluate the effects of the anti-serotonergic agent ketanserin, which has associated alpha 1-blocking properties, on IOP in normotensive and hypertensive eyes. The first part of the study was performed in six arterial hypertensive patients (mean +/- SD blood pressure 156/102 +/- 10/6 mmHg) with a pretreatment IOP in the normal range (15.7 +/- 1 mmHg). Both blood pressure and IOP were measured at baseline and at 1 hour intervals up to 3 hours following the oral administration of ketanserin 20 mg or placebo, given in a randomized manner. Three hours after ketanserin treatment, mean systolic and diastolic blood pressures dropped by 10/5 mmHg and mean IOP was reduced by 2.7 mmHg; after placebo, no change was observed in these variables. Thereafter, four normotensive patients with chronic open-angle glaucoma (IOP = 22.8 mmHg) were given 20 mg ketanserin orally. Three hours after administration, a 22% reduction in mean IOP occurred (-5.8 mmHg), with a concomitant reduction in mean systolic blood pressure of 13.0 mmHg. These results indicate that ketanserin treatment reduces IOP and systemic blood pressure. Further, long-term studies are needed in order to confirm the efficacy of ketanserin in the medical treatment of ocular hypertension.

Cardiovascular response to adrenergic stimulation during treatment with tertatolol. A new non-cardioselective beta-blocking agent in primary hypertensive patients.

The antihypertensive effects of tertatolol, a new non-cardioselective beta-blocking drug, were investigated in 20 patients with mild to moderate primary arterial hypertension, in a placebo controlled double blind randomized study. After tertatolol 5 mg o.d. significant decreases in both systolic and diastolic blood pressure and in heart rate were observed at rest (BP from 155/103 +/- 3/1 to 139/91 +/- 4/3 mmHg p less than 0.01; HR from 79 +/- 2 to 60 +/- 2 bpm p less than 0.01). Peak blood pressure, heart rate and myocardial O2 consumption, indirectly measured as cardiac workload, determined during adrenergic stimulation by 70 degrees head-up tilt, cold pressor test, mental arithmetic stress, isometric exercise and bicycle exercise were also reduced by 4 weeks of tertatolol treatment in comparison to pretreatment levels. No significant changes in the same parameters were induced by placebo. No side effects were observed during treatment.

Interference by sulphinpyrazone with the antihypertensive effects of oxprenolol.

The interfering effect of sulphinpyrazone, a uricosuric agent which reduces the activity of cyclo-oxygenase, with the antihypertensive activity of oxprenolol, a non-cardioselective beta-blocker with sympathomimetic activity, has been evaluated. Ten patients with primary arterial hypertension of mild to moderate degree entered a randomized double-blind cross-over study versus placebo. They were given oxprenolol + placebo or oxprenolol + sulphinpyrazone for 15 days, and then the treatments were crossed-over for a further 15 days. Oxprenolol significantly reduced blood pressure (161 +/- 3/101 +/- 1 vs 149 +/- 4/96 +/- 2 mmHg) and heart rate (72 +/- 3 vs 66 +/- 3 beats/min). During administration of the combination with sulphinpyrazone the blood pressure increased to its pretreatment level (156 +/- 5/101 +/- 2 mmHg). The effect of oxprenolol on heart rate was not influenced by the combined treatment (67 +/- 6 beats/min). The results may be explained by 1) sulphinpyrazone-induced inhibition of prostaglandin synthesis, which could interfere with the antihypertensive activity of oxprenolol, or 2) sulphinpyrazone-induced acceleration of the metabolism of oxprenolol.

Antihypertensive efficacy of the combination of ketanserin + thiazide in hypertensives older than 50 years.

The antihypertensive effect of the combination of ketanserin, a new antiserotonergic agent, and thiazide has been evaluated in 35 patients with arterial hypertension of mild to moderate degree in the greater than 50-year-old age group. Twenty patients were given ketanserin (20 mg) + hydrochlorothiazide (25 mg) (treatment A) while the others were given ketanserin (40 mg) + hydrochlorothiazide (12.5 mg) (treatment B) once daily, for a period of 6 weeks. Twenty-four-hour blood pressure, measured by an automatic recorder, was significantly reduced by both combinations. In particular, treatment A reduced blood pressure from 169 +/- 15/95 +/- 6 mm Hg before treatment to 146 +/- 11/83 +/- 8, 149 +/- 13/82 +/- 10, 143 +/- 12/81 +/- 9, and 151 +/- 14/84 +/- 7 mm Hg at 2, 6, 8, and 24 h, respectively, after the last dose of drug. With treatment B, blood pressure was reduced from 167 +/- 11/97 +/- 7 mm Hg before treatment to 152 +/- 12/89 +/- 8, 151 +/- 15/85 +/- 8, 150 +/- 16/86 +/- 8, and 158 +/- 13/91 +/- 7 mm Hg at 2, 6, 8, and 24 h, respectively. Heart rate was not affected by both treatments despite the fact that ketanserin has been proved to induce a marked vasodilation. Cardiac workload (systolic blood pressure X heart rate) was slightly reduced by the treatments. Treatment A only induced transient dizziness after the first dose of drug; treatment B, on the other hand, induced drowsiness and more marked dizziness, which in one case was also observed after repeated doses of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular mass and blood pressure during ergometric exercise in primary hypertension.

The pathophysiology of left ventricular hypertrophy (LVH) in hypertensive patients is still an intriguing point. The lack of a close relationship between LVH and systolic or diastolic blood pressure at rest, previously observed by other investigators, was confirmed in our group of 45 patients with uncomplicated primary hypertension. The strength of correlation between echocardiographic left ventricular mass (LVMe) and blood pressure, expressed as incremental area (IA = total area under the curve--basal area), however, increased during bicycle exercise testing (r = 0.33, p less than 0.05 for diastolic blood pressure; r = 0.39, p less than 0.01 for systolic blood pressure; r = 0.41, p less than 0.01 for mean arterial pressure). Other echocardiographic parameters of myocardial mass such as LVM index (LVMI) and septal thickness (ST) were also significantly correlated with blood pressure during exercise. These results suggest either that blood pressure during exercise is a better index of the cardiac workload than resting blood pressure or that the pathogenesis of cardiac hypertrophy involves an enhanced reactivity to adrenergic drive, particularly stimulated during ergometric exercise. Increased blood pressure alone, however, only partly accounts (about 20%) for the increase in myocardial mass in hypertensive patients; other factors, therefore, need to be further investigated for a better understanding of the pathophysiology of left ventricular hypertrophy.

Cardiovascular response to mental stress and to handgrip in children. The role of physical activity.

Cardiovascular responses to sympathetic stimulation may be altered in the early phases of life of subjects with a family history of hypertension. The possible influence of physical activity on adrenergic modulation in children is still not well known. In this study we evaluated, in a group of 162 11-year-old children from a secondary school near Naples, blood pressure and heart rate measured 4 times at 3-week intervals at rest and during adrenergic system stimulation by mental arithmetic stress and isometric exercise. Children were divided into sedentary and physically active groups according to the levels of a Saltin modified questionnaire. Family history of hypertension was also investigated. Systolic and diastolic blood pressure at rest were slightly higher in the sedentary group at each control (107/75 +/- 11/11 vs 105/73 +/- 11/11 mmHg at the first and 100/70 +/- 14/14 vs 98/69 +/- 9/9 at the last control); heart rate in the same group was higher as well (91 +/- 11 vs 87 +/- 12 beats/min, p less than 0.02 at the first and 80 +/- 9 vs 77 +/- 11 at the last control). Systolic and diastolic blood pressure increased by 7/15% during mental stress and by 23/45% during isometric exercise in the sedentary group. The corresponding blood pressure increases in the physically active group were 6/12% and 20/40%, respectively. These responses were independent of sex, body weight and family history of hypertension. These results support the hypothesis that regular physical activity in young adolescents only mildly influences resting blood pressure and cardiovascular responses during the stimulation of the sympathetic nervous system.

Effect of oral ketanserin administration on intraocular pressure in glaucomatous patients.

We evaluated the effect of the antihypertensive drug ketanserin, a 5-HT antagonist, on intraocular pressure (IOP) in 20 patients with ocular hypertension. IOP, pupil diameter, systolic arterial pressure (SBP), diastolic arterial pressure (DBP) and heart rate (HR) were recorded at baseline and at 1-hr intervals for 3 hr after oral administration of 20 mg ketanserin or placebo, given in a randomized, double masked, cross-over fashion. The alternative treatment was given a week later. In all patients, ketanserin significantly lowered IOP and SBP, while no variations in pupil diameter, DBP and HR were found. Moreover, after drug administration, total outflow facility, measured by conventional tonography, increased significantly. These findings indicate that oral ketanserin could represent a new antiglaucomatous drug.

Slow-release nifedipine versus placebo in the treatment of arterial hypertension. A double blind ergometric evaluation of cardiac workload.

The effects of slow-release nifedipine on blood pressure and cardiac workload have been studied during bicycle exercise testing in a randomized, double blind trial in 20 patients with mild to moderate hypertension. After a fortnight's wash-out, patients were allocated to either slow-release nifedipine (20 mg twice daily) or placebo for a 2-month period. At baseline and at the end of treatment blood pressure and heart rate were measured at rest and during ergometric exercise; cardiac workload was calculated as the product of systolic blood pressure by heart rate. Significant decreases in blood pressure at rest and in cardiac workload on exercise were demonstrated at the end of nifedipine treatment. The reduction of cardiac workload was mainly due to the lower baseline values of resting blood pressure. Heart rate showed a reduction of its increase during ergometric exercise at the end of nifedipine treatment as compared to baseline, likely due to an improvement in stroke volume.

Effects of sodium intake on blood pressure and adrenergic vascular reactivity.

The effects of dietary sodium restriction (approximately 2 g daily) on blood pressure (BP) and vascular reactivity to norepinephrine (NE) were evaluated in 12 patients with uncomplicated primary hypertension. BP was significantly reduced at the end of the treatment both at rest (153/100 +/- 19/7 vs. 142/93 +/- 19/5 mmHg) and during an exercise test on a bicycle. The pressor response to NE was significantly lower at the end of the low sodium period (reactivity index = 0.0044 vs. 0.0031; p less than 0.05): A twofold dose of NE was needed to increase mean BP by 20 mmHg (PD20) (from 273 +/- 120 to 450 +/- 218 ng/kg/min; p less than 0.05). Twenty-four-hour NE excretion increased significantly on a low-salt diet (40 +/- 14 vs. 49 +/- 16 micrograms/24 hr; p less than 0.05). The decrease in BP was inversely related to changes in PD20 (R = -0.60; less than p0.05). These results provide the evidence that the fall in BP is, at least in part, mediated by decreased end-organ responsiveness to adrenergic stimulation.