Maria Luisa Fasano

Changes in left ventricular mass during a double-blind study with chlorthalidone and slow-release nifedipine.

SummaryThe presence of a possible correlation between changes in left ventricular mass of hypertensive patients and the degree of blood pressure reduction with different antihypertensive drugs has been investigated in 40 outpatients by M-mode echocardiography. Ten of these, with blood pressure in normal limits with different antihypertensive treatment had their therapy changed in chlorthalidone 25 mg/day without any run-in (Group A); other 30 patients, with a previously uncontrolled blood pressure, after a 14 day run-in, were randomly allocated to chlorthalidone 25 mg/day (Group B), slow release nifedipine 20 mg/day (Group C) or placebo (Group D). At the end of the eight week treatment period a further decrease in systolic blood pressure was observed in Group A without changes in ventricular mass; an highly significant decrease in both systolic and diastolic blood pressure was observed in B and C but only patients on chlorthalidone changed their ventricular mass; no change in both blood pressure and ventricular mass was observed on placebo. As changes in ventricular mass are not correlated with blood pressure reduction, we conclude that other, not well defined factors, apart from the decrease in duration and degree of left ventricular systolic wall tension, may be responsable for reversal of left ventricular hypertrophy.

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 × 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 < 0.001) and during exercise in subjects receiving nitrendipine, while placebo did not modify these parameters. LVMe (from 195 to 188 gm; P < 0.01) and CSA (from 20.2 to 19.8 cm2; P < 0.05) were reduced by nitrendipine, which also improved cardiac performance (ESV fell from 44 to 38 ml [P < 0.001] and EF fell from 62% to 66% [P < 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.

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

SummaryThe 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<0.001) and diastolic (106±8 vs 93±3 mm Hg, p<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<0.001 as absolute reduction; r=0.791, p<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.

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: β‐agonist activity, β1‐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.

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.

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 >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 × 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. These data, therefore, support the hypothesis that the combination of ketanserin + thiazide, particularly at the dose of 20 + 25 mg, respectively, is an effective and well-tolerated antihypertensive treatment in patients in the >50-year-old age group.

Interference by sulphinpyrazone with the antihypertensive effects of oxprenolol

SummaryThe 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 doubleblind 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.

Response to tilting in hypertensive patients receiving ketanserin

Ketanserin is an investigational antiserotonergic agent, recently proved to be effective in the treatment of hypertension [1, 2]. It has been suggested that it may reduce blood pressure by affecting alphal-adrenergic receptors as well as 5-HT2 receptors [3-5]. In a personal study of oral ketanserin 40 mg b.d. it was shown that the antihypertensive effect at the beginning of treatment was concomitant with symptoms of orthostatic hypotension [6]. In order to investigate whether the orthostatic effects of ketanserin also appear at a lower dose, a recent acute study has been done on 24-h pressor response to ketanserin 20 mg, particularly evaluating the cardiovascular response to 70 ° head-up tilt in a group of 8 (4M, 4F; age range 50-74 years) mild or moderate hypertensive patients. Blood pressure and heart rate were measured hourly with an automatic recorder (Sentron, Bard Biomedical), with the subjects supine and after 5 min head-up tilt. Supine blood pressure was significantly reduced by ketanserin up to 8h ( 1 6 4 _ 1 1 / 9 3 _ 6 m m H g at baseline, 144_ 14/85 _ 6 mmHg after 2 h and 149 _ 18/83 _ 5 mmHg after 8 h; the corresponding heart rates were 67+9, 64_+11 and 66_+8 beats/min, respectively). During 70 ° head-up tilt 6patients showed the same blood pressure changes from the supine levels both during and before administration of ketanserin (Fig.l). Two patients complained of symptoms of orthostatic hypotension between l and 6 h after dosing and were not tilted. Thus, the antihypertensive effect of ketanserin was observed in 6 out of 8 patients given 20 mg without impairment of the pressor response to tilting. Therefore, its antihypertensive activity appears to depend on more than one mechanism regulating blood pressure. In addition to its antiserotonergic activity,