Biomedical subjects

G Leonetti

Publications and source records attributed to G Leonetti.

At least 127 records · Page 7Linked to original sources

PubMed1990

Natriuretic effects of calcium antagonists. Clinical implications.

An important characteristic which distinguishes calcium antagonists from traditional vasodilators is their natriuretic rather than antinatriuretic action. Evidence that all classes of calcium antagonists have a natriuretic effect has been provided by intravenous administration in animal experiments. After single oral doses, all calcium antagonists have some natriuretic effect, but its extent differs with different compounds; dihydropyridines have a greater immediate natriuretic response than verapamil or gallopamil. Recent experiments by our group using the newer dihydropyridine derivative, isradipine, indicate that the natriuretic response may occur at even lower doses than the antihypertensive effect. Indeed, doses of 2.5mg, 5.0mg and 7.5mg of this compound caused an increasingly larger fall in blood pressure, while the natriuretic and diuretic effects peaked with the 2.5mg dose. The natriuretic effect is associated with no or a very small change in glomerular filtration rate and with a more consistent increase in renal plasma flow. The duration of the natriuretic action of calcium antagonists is debated. Our studies have shown that this action is evident during the first 2 days of administration of a dihydropyridine, and then seems to disappear; however, a small negative sodium balance persists, an observation that accounts for the absence of any increase in bodyweight or fluid volumes with long term administration of calcium antagonists, despite their vasodilating action. Recent data have shown that under long term treatment with isradipine sodium clearance was still increased a few hours after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

The effects of nicardipine in elderly hypertensive patients.

Hypertension becomes more prevalent with advancing age, and the hemodynamic pattern differs from that in younger patients. In the elderly, elevated blood pressure is primarily due to reduced compliance of large vessels, resulting in an increase in total peripheral resistance, but in younger subjects it mainly reflects an increase in cardiac output. Vasodilator drugs, such as calcium antagonists, might therefore be expected to be particularly effective in lowering blood pressure in the elderly. Clinical experience has confirmed the safety and antihypertensive efficacy of these drugs, with some workers suggesting that calcium antagonists are particularly effective in the elderly. A 6-month multicenter study involving 2,184 patients has shown a direct correlation between pretreatment blood pressure and the degree of blood pressure reduction observed during nicardipine treatment with or without other antihypertensive drugs. Isolated systolic hypertension was significantly reduced but diastolic blood pressure was not affected. The incidence of side effects among elderly hypertensive patients, both with and without concomitant disease, was slightly lower than in younger patients.

Adolescent↗

PubMed1990

[Morphofunctional characteristics of the left ventricle in arterial hypertension: echocardiographic and Doppler study].

The role of arterial hypertension in the development of left ventricular hypertrophy is well documented; in contrast, the characteristics of the right ventricle in this condition are poorly defined. To investigate whether structural and functional changes of the right ventricle are associated with systemic hypertension, we studied a total of 105 patients using M-mode, 2D and pulsed-Doppler echocardiography. Of these, 31 were hypertensive patients with left ventricular hypertrophy (III), 42 were hypertensives without left ventricular hypertrophy (II) and 32 were normotensive controls (I). Right ventricular anterior wall thickness was measured from the parasternal window, in long axis. The following left and right ventricular filling parameters were evaluated using Doppler mitral and tricuspid flow analysis: the early (E) and late (A) peak velocity, the ratio E/A. Our results show that: right ventricular anterior thickness was 5.7 +/- 0.9 mm in III, 4.3 +/- 0.8 in II and 3.7 +/- 0.8 in I (p less than 0.05 II vs I, p less than 0.01 III vs II and I). There is a significant correlation between right and left ventricular wall thickness in the hypertensive population (r = 0.75, p less than 0.01). Left ventricular filling shows a progressive reduction in E and an increase in A with a progressive reduction in the E/A ratio from 1.47 in I to 1.31 in II and 0.78 in III. Similarly E/A ratio for right ventricular filling decreases from 1.70 in I, 1.32 in II and 0.92 in III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

[The characteristics of left ventricular filling in a mild grade of physiological and pathological hypertrophy. A Doppler echocardiographic study].

The aim of this study was to evaluate diastolic function in athletes and in young borderline hypertensives with mild left ventricular hypertrophy. To compare the effects on left ventricular filling of these two conditions we studied 15 borderline hypertensives (age 21 +/- 3 yrs, left ventricular mass index 137 +/- 9 g/m2), 18 soccer players (age 22 +/- 4 yrs, left ventricular mass index 136 +/- 12 g/m2) and 20 normotensive subjects (age 22 +/- 4 yrs, left ventricular mass index 94 +/- 10 g/m2) using the echo-Doppler technique. Left ventricular mass (LVM) was calculated with Devereux's formula. The criterion for left ventricular hypertrophy was left ventricular mass index greater than or equal to 120 g/m2. The following parameters of left ventricular filling were evaluated by Doppler transmitral flow analysis: the early (E) and late (A) peak velocity, the ratio E/A, the integral of early (Ei) and late (Ai) diastolic velocity. We concluded that the left ventricular filling profile was similar in borderline hypertensives, in athletes and in normotrophic subjects. These findings suggest that at least in its early stages, mild cardiac hypertrophy secondary to pathological stimulus is characterized by indices of diastolic function which are no different to those found in athletes with physiological hypertrophy.

Adult↗

PubMed1990

Evaluation of the efficacy and safety of enalapril plus hydrochlorothiazide plus methyldopa vs standard triple therapy in the treatment of moderate to severe hypertension: results from a multicentre study.

We report the results of a randomized, double-blind, parallel group multicentre study in 120 patients with moderate to severe hypertension, comparing two different types of antihypertensive treatment: a) the standard 'triple therapy' with hydrochlorothiazide, propranolol and hydralazine, and b) the combination of an ACE inhibitor, enalapril with hydrochlorothiazide (HCTZ) and methyldopa. The two regimens caused similar degrees of blood pressure reductions. The only significant difference between the two groups was heart rate due to the bradycardiac effect of propranolol in the group treated with the standard 'triple therapy'. Only 3.4% of patients receiving the regimen of enalapril, HCTZ and methyldopa were withdrawn from the study for adverse reactions, against 10% of patients on HCTZ, propranolol and hydralazine. Four cases of hypokalaemia in the enalapril group and 19 in the propranolol group were reported: so enalapril seemed to ameliorate the hypokalaemic effect of HCTZ. The overall analysis of the study results shows that the treatment based on enalapril, HCTZ and methyldopa is as efficient and better tolerated than the established regimen of HCTZ, propranolol and hydralazine.

Blood Pressure↗

PubMed1989

Relation between mortality and treated blood pressure in elderly patients with hypertension: report of the European Working Party on High Blood Pressure in the Elderly.

OBJECTIVE: To investigate the relation between mortality and treated systolic and diastolic blood pressures. DESIGN: Randomised double blind placebo controlled trial. Mortality in the two treatment groups was examined in thirds of treated systolic and diastolic blood pressures. PATIENTS: 339 And 352 patients allocated to placebo and active treatment, respectively. The groups were similar at randomisation in sex ratio (70% women), mean age (71.5 years), blood pressure (182/101 mm Hg), and proportion of patients with cardiovascular complications (35%). MEASUREMENTS AND MAIN RESULTS: In the placebo group total mortality rose with increasing systolic pressure whereas it had a U shaped relation with diastolic pressure, the total lowest mortality being in patients in the middle third of the distribution of diastolic pressure. In the group given active treatment total mortality showed a U shaped relation with systolic pressure and an inverse association with treated diastolic pressure. In both groups cardiovascular and non-cardiovascular mortality followed the same trends as total mortality. The increased mortality in the lowest thirds of pressure was not associated with an increased proportion of patients with cardiovascular complications at randomisation or with a fall in diastolic pressure exceeding the median fall in pressure in each group. In contrast, patients in the lowest thirds of pressure showed greater decreases in body weight and haemoglobin concentration than those in the middle and upper thirds of pressure. CONCLUSIONS: In patients taking active treatment total mortality was increased in the lowest thirds of treated systolic and diastolic blood pressures. This increased mortality is not necessarily explained by an exaggerated reduction in pressure induced by drugs as for diastolic pressure a U shaped relation also existed during treatment with placebo. In addition, patients in the lowest thirds of systolic and diastolic pressures were characterised by decreases in body weight and haemoglobin concentration, and the patients in the lowest thirds of diastolic pressure taking active treatment also by an increased non-cardiovascular mortality, suggesting some deterioration of general health.

Aged↗

PubMed1989

Cardiovascular and renal effects of single administration of three different doses of isradipine in hypertensive patients. Dose-response curves of the different effects.

The antihypertensive, humoral, and renal effects of acute single oral administration of placebo and isradipine, a new dihydropyridine calcium antagonist, at doses of 2.5 mg, 5.0 mg, and 7.5 mg once daily were investigated in 11 patients with mild-to-moderate uncomplicated essential hypertension. The patients maintained a constant daily intake of 100 mmol of sodium and 40 mmol of potassium. Placebo and isradipine were randomly administered to each patient, according to a Latin-square design, at intervals of at least 48 hours. The antihypertensive effect was dose-dependent and peaked at two hours after oral administration; changes at the lowest dose were already statistically significant (p less than 0.01). Increases in heart rate were mild and similar with all isradipine doses. Glomerular filtration rate and renal plasma flow showed a trend towards a dose-dependent rise; plasma renin activity was statistically increased (p less than 0.05) following the highest isradipine dose, whereas plasma aldosterone was unmodified. Isradipine resulted in a statistically significant rise (p less than 0.05) in sodium excretion and urine volume, which was similar with all active doses. In conclusion, the antihypertensive efficacy of isradipine is dose-dependent, whereas the natriuretic and diuretic effects are already at maximum following 2.5 mg per day, the lowest dose in this study.

Antihypertensive Agents↗

PubMed1989

The clinical performance of nicardipine in elderly hypertensive patients with concomitant diseases.

The efficacy and tolerance of nicardipine were evaluated in 2184 ambulatory hypertensive patients with or without concomitant diseases in a 24-week Italian multicenter study. Of the total patient group 1083 had one or more concomitant diseases (diabetes mellitus, coronary heart disease, cardiac failure, mild renal failure, chronic cerebrovascular disease, obstructive lung disease, and peripheral vascular disease); of these patients, 419 were aged over 65 years. Patients were seen on an outpatient basis and after a 2- to 4-week washout period were admitted to the study. The initial nicardipine dose of 20 mg three times a day was titrated in subsequent weeks; thereafter a second antihypertensive drug was added if seated diastolic blood pressure was not reduced below 90 mm Hg. The nicardipine-based therapy significantly lowered seated blood pressure in the whole population (mean 185/102 to 152/86 mm Hg) without clinically and statistically significant differences between the patient subgroups with concomitant diseases. There were no changes in either symptoms, or biochemical and instrumental tests of the concomitant diseases. The incidence of side effects was low; in particular, there was no orthostatic hypotension. Nicardipine-based treatment is therefore effective, safe, and well tolerated in elderly hypertensive patients with concomitant disease.

Aged↗

PubMed1989

Advantages and limitations of diuretic therapy in essential hypertension.

The diuretics previously considered the "cornerstone" of the antihypertensive treatment have recently undergone a reevaluation and have been considered as a potential cause of the lack of "cardioprotection" found in different epidemiological studies. The reduction in plasma potassium and the changes in lipoproteins should represent the mechanisms of the negative interference of diuretics at cardiac levels. In spite of this common opinion, there is no clinically consistent evidence that the lowering of serum potassium and the changes in lipoproteins are responsible for the lack of cardioprotection during antihypertensive therapy. It is possible that other causes, for instance the reflex activation of sympathetic nervous system and/or renin secretion, may play an important role in determining the cardiac effects of antihypertensive therapy. However, it is also true that diuretics have been used in the past at doses that were too high, and the changes in serum potassium and lipoproteins can be minimized by administering lower doses of diuretics without decreasing their antihypertensive efficacy.

Benzothiadiazines↗

PubMed1989

Nadolol prevents the exercise-induced rise in lymphocyte beta-receptor number in borderline hypertension.

Thirteen borderline hypertensives were investigated at rest and during dynamic exercise, before and after therapy with nadolol (40-80 mg/day for 7-28 days), in order to evaluate regulation of the number of lymphocyte beta-receptors. Systolic blood pressure and the heart rate were measured before and after 15 min of bicycle exercise, both with and without nadolol therapy; blood samples were withdrawn for adrenaline, noradrenaline and lymphocyte beta-receptor determinations. Nadolol induced a significant decrease in systolic blood pressure and the heart rate at rest, while plasma catecholamines and lymphocyte beta-receptors did not change significantly. Of the physiological responses to dynamic exercise (increases in systolic blood pressure, heart rate, plasma noradrenaline levels and adrenaline and lymphocyte beta-receptors), only the rise in beta-receptors was entirely prevented, and the increase in the heart rate was significantly attenuated by nadolol. It is suggested that the lack of a rise in the number of beta-receptors during exercise may contribute to the blunted exercise-induced tachycardia in patients taking nadolol.

Adult↗

PubMed1989

Right ventricular wall thickness and function in hypertensive patients with and without left ventricular hypertrophy: echo-Doppler study.

The structure and function of the right ventricle in arterial hypertension have been the subject of only a few reports. The present study evaluated the functional and structural changes in both left and right ventricles. Doppler and standard echocardiography were performed in 58 hypertensive patients (33 without and 25 with left ventricular hypertrophy). We concluded that right ventricular wall thickness is significantly increased in hypertensive patients compared with normotensive subjects, and that there is a significant, direct correlation between right and left ventricular thickness. Abnormalities in right and left ventricular filling, characterized by a reduction in early and an increase in late diastolic flow velocity, occur in hypertensive patients, and there is a direct correlation between late mitral and tricuspidal flow velocities and left and right ventricular thickness.

Adult↗

PubMed1989

Nicorandil, a new vasodilator drug, in patients with essential hypertension.

In 12 mild to moderate hypertensive patients we investigated the acute antihypertensive efficacy of three different doses of nicorandil, a new vasodilating agent which probably acts by increasing the potassium efflux from smooth muscle cells and causing a cellular hyperpolarization. After a 3-day placebo period the patients were given, according to a double-blind Latin-square randomized design, 10, 20 and 30 mg nicorandil as a single acute dose every other day. Blood pressure and the heart rate were measured in both supine and upright positions at various times for 24 h after the dosing; fractional urine collections were obtained at the end of the placebo period and after each active dose. All doses of nicorandil similarly and significantly (P less than 0.01) reduced supine blood pressure, with a peak after 4-6 h (10 mg: -21/-8 mmHg; 20 mg: -20/-9 mmHg; 30 mg: -29/-17 mmHg), and the effect was still present, though reduced, after 24 h; no change in the heart rate was observed. The results from the upright position were similar. There were no significant changes in urine volume and electrolyte excretion during the nicorandil administration. The three different doses of nicorandil caused similar acute blood pressure reductions without change in the heart rate, nor in the urine volume and urinary sodium.

Adult↗

PubMed1989

Antihypertensive efficacy and influence on physical activity of three different treatments in elderly hypertensive patients.

The antihypertensive efficacy and subjective and physical tolerability of three different pharmacological treatments (metoprolol, captopril and the combination of hydrochlorothiazide + amiloride) were compared with placebo in 36 elderly hypertensives (aged 61-79 years), according to a Latin-square double-blind design. The placebo and the active treatments were administered for 2 months. Seated blood pressure was significantly reduced by all the pharmacological treatments compared with placebo, but only metoprolol significantly reduced the heart rate. No haematological or biochemical changes were observed during the study. Physical fitness, evaluated as endurance in a standard cycle ergometer exercise test, was slightly decreased after the treatment with metoprolol and the diuretic combination and slightly improved after treatment with captopril. Subjective tolerability, evaluated by a check-list of symptoms, was better during the active therapies, and in particular during the captopril treatment, than during the placebo treatment. Our results indicate that all three active treatment regimens significantly reduce blood pressure in elderly hypertensives and that captopril appears slightly better tolerated physically and subjectively.

Aged↗

PubMed1989

[Pulsed Doppler evaluation of left ventricular filling in stable and borderline juvenile arterial hypertension].

Left ventricular hypertrophy in hypertensive patients may be associated with changes in diastolic function. To examine whether or not any alteration in left ventricular function is also present in the early phases of hypertension, left ventricular filling was studied using the echo-Doppler method in 30 young mild hypertensive patients, 40 borderline untreated hypertensives and 30 age-matched normotensive controls. Left ventricular wall thickness, left ventricular mass (Dévereux formula) and shortening fraction were measured using M-mode echocardiogram under 2D control. Trans-mitral flow was measured by pulsed-Doppler and the following parameters were derived: peak early (E) and atrial (A) diastolic flow rate, their ratio E/A, the integral of early (Ei) and atrial (Ai) diastolic flow rates and their ratio (Ei/Ai). Our data show that left ventricular mass is greater in mild hypertensive patients than in borderline and normal controls. No differences in left ventricular systolic function were found in the three groups whereas diastolic function changes were present in the hypertensive group: in particular the peak early/atrial flow rate ratio was significantly reduced compared with the other two groups. Therefore, it appears that changes in diastolic function may also be present even in the early phases of mild hypertension.

Adult↗

PubMed1988

Tolerability and well-being with indapamide in the treatment of mild-moderate hypertension. An Italian multicenter study.

Since hypertension is an important risk factor of cardiovascular morbidity and mortality that can be at least in part decreased by pharmacologic reduction in elevated blood pressure, it is necessary that an antihypertensive agent be effective, but at the same time well tolerated and, according to some recent hypotheses, have no deleterious effect on serum electrolyte levels, as well as lipoprotein and glucose tolerance. However, due to different cultural and social backgrounds, lifestyles, and so on, the tolerability may differ from one population to another and the conclusions drawn from a population cannot be extrapolated to people of other countries. For these reasons, the well-being of patients, as well as the tolerability of indapamide, a non-thiazide diuretic, have been investigated in patients with hypertension of mild and moderate degree from different parts of Italy with a satisfactory blood-pressure response to this drug (-22.8 +/- 0.6/-17.1 +/- 0.5 mm Hg). Simultaneous to the significant blood-pressure reduction, the only significant change among the metabolic effects was a slight reduction in plasma potassium levels (-0.37 +/- 0.03 meq/liter). The tolerability was, on the whole, very good with a tendency toward an improvement of well-being in patients, the majority of whom were already asymptomatic before starting the treatment.

Adult↗

PubMed1988

Antihypertensive efficacy of nicardipine-based treatment in patients of different age and in patients with isolated systolic hypertension.

The relationship between age and the antihypertensive efficacy of calcium antagonists has been investigated by different authors with conflicting results. In order to evaluate this relationship an Italian multicentre study investigated 2184 patients with mild to moderate hypertension with an age range of 24-90 years. Initial treatment consisted of nicardipine monotherapy (daily dose 40-80 mg/day in two or three oral administrations); after 4 weeks other antihypertensive agents could be added in non-responders (seated blood pressure greater than 160/95 mmHg). The patients were divided into four groups according to age (less than or equal to 55 years, 56-65 years, 66-75 years and greater than 75 years). Nicardipine-based treatment reduced systolic and diastolic blood pressures to similar levels independently of the age of the patients. The correlation between systolic blood pressure reduction and age was only 0.141 (NS). The percentage of patients treated with nicardipine monotherapy was similar in all age groups, but the incidence of side effects, mostly transient and mild, was lower in older than in younger patients. In patients older than 65 years with isolated systolic hypertension (systolic pressure greater than 160 and diastolic pressure less than 90 mmHg), nicardipine-based therapy significantly lowered systolic blood pressure only from 180 +/- 11/87 +/- 6 to 148 +/- 14/84 +/- 8 mmHg.

Age Factors↗

PubMed1988

Nifedipine does not blunt the aldosterone and cardiovascular response to angiotensin II and potassium infusion in hypertensive patients.

The antihypertensive response of calcium antagonists of the dihydropyridine series, although accompanied by a significant increase in plasma renin activity (PRA), is generally not associated with a comparably significant rise in plasma aldosterone (PA). This has been suggested to be due to the adrenal glomerular cell responsiveness being dependent on calcium entry. To investigate this hypothesis, angiotensin II (AII; 0.15, 0.375, and 0.750 micrograms/min, each step for 20 min) and KCl (30 mmol/50 min) were infused on separate days in 11 hypertensive patients kept at a constant daily intake of 100 mmol sodium and 40 mmol potassium, before and after 1 week of nifedipine treatment (20 mg b.i.d.). Supine blood pressure (BP) was significantly (p less than 0.01-p less than 0.001) reduced after nifedipine treatment; supine PRA increased significantly (p less than 0.01), while PA did not change significantly. No change in plasma potassium level was seen during nifedipine treatment. The dose-dependent mean BP rises induced by AII were slightly blunted during nifedipine treatment, whereas the PRA decreases and the PA rises after the peak infusion were not significantly different before and during nifedipine administration. Potassium infusion had no significant effect on BP, and caused a significant and similar rise in PA before and during nifedipine administration, while PRA decrease was more pronounced after nifedipine treatment. As previously shown in normotensive subjects, and also in hypertensive patients, aldosterone responses to two major stimulants, such as AII and potassium, do not appear to be blunted by treatment with a calcium antagonist.

Adult↗

PubMed1988

Effects of alpha-adrenoceptor blockers on renal function and blood pressure adjustment in human hypertension.

In this paper the different aspects of the role played by alpha-adrenoceptors in the control of renin secretion from the juxtaglomerular apparatus and renal sodium and water reabsorption, and the effects of alpha-adrenoceptor antagonists on systemic haemodynamics, will be investigated. Animal experiments suggest that the renal alpha-adrenoceptors exert a restraining action on renin secretion while increasing tubular reabsorption of sodium and water. A recent study in man has confirmed the alpha-adrenoceptor-mediated inhibition of renin secretion. Previously available ganglion blocking and antiadrenergic agents, while causing a significant supine blood pressure reduction, can cause at the same time clinically relevant side effects such as orthostatic hypotension, sedation, drowsiness etc. The advent of selective alpha 1-adrenoceptor blockers, such as prazosin and urapidil, allow a significant blood pressure reduction without significant interference on haemodynamic adjustments and only induce a limited incidence of side effects.

Adrenergic alpha-Antagonists↗