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Biomedical subjects

G Leonetti

Publications and source records attributed to G Leonetti.

At least 145 records · Page 8Linked to original sources

Centrally acting antihypertensive agents.

In spite of the fact that plasma catecholamine levels, baroreflex activity, and hemodynamic pattern significantly change with age and drugs whose action is mediated via the sympathetic nervous system might be expected to cause different effects, the limited available data suggest that both alpha-methyldopa and clonidine lower blood pressure to a similar extent in young, middle-aged, and old patients. However, in the great majority of published works, only the mean or the range of the age are reported; therefore, it is difficult to compare the antihypertensive efficacy of the centrally acting drugs to the age of the individual patient. However, the blood pressure reduction with both drugs is significantly correlated to the pretreatment blood pressure values. Clearly, this area of risk versus benefit of centrally acting drugs has not been adequately investigated, and it is unlikely that this will happen in the future.

Aged↗

Systemic haemodynamic and humoral changes during urapidil treatment in hypertensive patients.

Urapidil, a new antihypertensive agent exerting a peripheral alpha 1-postsynaptic blocking action and an additional action at the central level, has some characteristics which may correct the underlying pathophysiological abnormalities found in the great majority of hypertensive patients. When administered acutely and chronically, urapidil significantly lowers blood pressure in hypertensive patients by reducing total peripheral resistance, while cardiac output is unchanged or only slightly elevated. The blood pressure reduction can cause a decrease in cardiac mass in patients with left ventricular hypertrophy. Urapidil has been successfully administered also in patients with congestive heart failure and in hypertensive crises during or following surgical procedures; in all these conditions urapidil lowers total peripheral resistance, but blood pressure is lowered only in patients with hypertensive crises and no clinically relevant reduction in blood pressure is found in patients with congestive heart failure. The acute administration of urapidil has shown a trend towards a rise in plasma renin activity, in plasma aldosterone and in plasma catecholamines; on the whole, however, the activation of these systems has been mild.

Adrenergic alpha-Antagonists↗

[Correlation between arterial pressure at rest and during effort and left ventricular mass in hypertensive patients who were never treated].

A poor correlation has been found between blood pressure at rest and left ventricular mass in the course of several echocardiographic studies on hypertensive patients. The aim of this work was to determine if this finding could be the result of previous antihypertensive therapy, which had been suspended a few weeks previously in most of the studies. In addition, we tested whether blood pressure values during physical exercise correlate with the echocardiographic indices of left ventricular mass better than the values at rest. In our group of 43 patients with mild to moderate essential hypertension who had never been pharmacologically treated, the correlation between both systolic and diastolic blood pressure and left ventricular mass was poor (r = 0.41 and 0.30 respectively). This result suggests that one or more factors other than hypertension may determine the development of left ventricular hypertrophy. However, in 10 patients with left ventricular hypertrophy a more significant correlation was found between cardiac mass and diastolic pressure (r = 0.52), rather than systolic pressure (r = 0.33). This finding supports data indicating that cardiovascular risk is related more to diastolic pressure increments than to systolic pressure. As for blood pressure values during physical exercise, in our study they did not show a better predictivity of ventricular mass than the values at rest.

Adult↗

Effects of moderate low sodium/high potassium diet on essential hypertension: results of a comparative study.

It is generally accepted that a significant restriction in sodium intake can lower blood pressure in hypertensive patients and more recently it has also been suggested that a high potassium intake can exert an antihypertensive effect. We have therefore, conducted a double-blind, randomized, cross-over study to evaluate the antihypertensive efficacy of the combination of a modest dietary sodium restriction and a high potassium intake in hypertensive patients of mild and moderate degrees. During the modest sodium (100 mmol/day)/high potassium (130 mmol/day) diet the blood pressure was significantly reduced (-17/-6 mmHg) when compared to the normal diet (160 mmol Na/day and 80 mmol K/day). The blood pressure reduction did not interfere with hemodynamic and humoral responses to dynamic exercise. The modest reduction in sodium intake and increase in potassium content in the diet was well tolerated by the patients.

Adult↗

Effects of a low-sodium diet on antihypertensive and natriuretic responses to acute administration of nifedipine.

This study was designed to determine (1) whether different sodium intakes influence the acute antihypertensive effect of a single dose of nifedipine, (2) whether the combination of nifedipine and a low-sodium diet lowers blood pressure to a greater extent than administration of nifedipine alone and (3) whether a reduction in sodium intake can dissociate the antihypertensive from the natriuretic response to nifedipine. We studied 11 hypertensive patients in order to investigate the antihypertensive and natriuretic effects of a single oral dose of 10 mg nifedipine during sodium repletion (100 mmol/day sodium intake) and depletion (20 mmol/day sodium intake), with a constant potassium intake (40 mmol/day). Nifedipine significantly (P less than 0.01) lowered supine blood pressure, from 178 +/- 14/107 +/- 7 to 161 +/- 12/100 +/- 7 mmHg during sodium repletion and from 152 +/- 12/95 +/- 9 to 142 +/- 11/90 +/- 8 mmHg with sodium depletion. The natriuretic and diuretic actions of nifedipine were marked and statistically significant during sodium repletion and almost absent during sodium depletion. We conclude that (1) the acute antihypertensive effect of a single dose of nifedipine is present both in the sodium-replete and in the sodium-depleted states, although during sodium depletion the nifedipine effect is somewhat reduced in extent and duration; (2) the blood pressure reached after administration of nifedipine in the sodium-depleted state is significantly lower than the values reached after nifedipine treatment in the sodium-replete state; (3) the natriuretic action of calcium antagonists is not essential to the acute antihypertensive action of these compounds.

Adult↗

Calcium antagonists and responsiveness of the adrenal glands to aldosterone-releasing stimuli in hypertensive patients.

This study was designed to determine whether a reduced responsiveness of adrenal zona glomerulosa to physiological stimuli could be responsible for the lack of a proportional rise in plasma renin activity and plasma aldosterone during administration of calcium antagonists. We selected 11 hypertensive patients and measured the rise in plasma aldosterone in response to infusions of angiotensin II or potassium chloride before and after a 7-day treatment with fully antihypertensive doses of nifedipine (20 mg twice a day), while the patients were kept on a constant daily intake of sodium (100 mmol) and potassium (40 mmol). The treatment with nifedipine induced a significant reduction in both systolic and diastolic blood pressures; the infusions of angiotensin II (0.150, 0.375 and 0.750 microgram/min, each rate for 30 min) and of potassium chloride (50 mmol in 500 ml of 5% glucose in 50 min) caused similar rises in plasma aldosterone before and during the administration of the calcium antagonist. Therefore, our results indicate that responsiveness of the adrenal zona glomerulosa to physiological stimuli is maintained despite blockade of calcium channels capable of significantly lowering arterial blood pressure.

Adrenal Glands↗

Renal effects of felodipine in hypertension.

The results of 2 recent studies on the renal effects of felodipine in hypertensive patients are described. Antihypertensive doses of felodipine (10mg bid) displayed a clear natriuretic and diuretic effect associated with a constant glomerular filtration rate and an increase in renal plasma flow. With higher doses of felodipine (up to 50mg tid), the natriuretic effect was reversed to an antinatriuretic effect, accompanied by a reduction in glomerular filtration rate. The natriuretic effect of felodipine 10mg bid was evident during the first 2 days of administration, but a negative sodium balance was still present at the end of the seventh day. The mechanisms of the renal effects of calcium antagonists are discussed as well as the relevance of the natriuretic effect for the antihypertensive action of these compounds.

Antihypertensive Agents↗

Resting and postexercise hemodynamic effects of carvedilol, a beta-adrenergic blocker and precapillary vasodilator in hypertensive patients.

Carvedilol is a recently developed antihypertensive drug that combines in the same molecule a nonselective beta-adrenoceptor blocking effect and a vasodilating precapillary activity. In our study, we have investigated the effects of carvedilol 25 mg b.i.d. on blood pressure, heart rate, and plasma noradrenaline in hypertensive patients at rest and during exercise after acute and repeated oral administration for 7 days. The daily average supine blood pressure of the 12 patients with essential hypertension was 178 +/- 10/107 +/- 3 mm Hg (means +/- SD of 8 measurements in each patient) after placebo and was significantly (p less than 0.01) reduced to 162 +/- 17/99 +/- 8 mm Hg on the first day and to 158 +/- 15/96 +/- 8 mm Hg on the seventh day of carvedilol treatment. Similar values were found in the upright posture. Heart rate was slightly but significantly lowered during acute and repeated administration. The exercise-induced increase in systolic blood pressure was significantly reduced by carvedilol 25 mg b.i.d., while there was a nonsignificant reduction in the tachycardic response. There was a significantly greater rise in plasma noradrenaline during exercise on the seventh day of carvedilol treatment. Carvedilol significantly lowered blood pressure and heart rate at rest and the exercise-induced rise in systolic blood pressure.

Administration, Oral↗

Effects of different sodium intakes on the antihypertensive and renal effects of single oral doses of nifedipine in hypertensive patients.

The aim of this study was to investigate whether the antihypertensive and renal effects of Ca2+ antagonists are related to the sodium state of the patients. For this purpose, in a group of 11 patients with essential hypertension we have compared the blood pressure lowering effects of a single oral dose of nifedipine before (100 mmol Na+/day and 40 mmol K+/day) and after sodium depletion (20 mmol Na+/day and 40 mmol K+/day: each period was of 6-8 day duration). During the normal sodium diet nifedipine significantly lowered supine blood pressure (from 185 +/- 13/107 +/- 7 to 161 +/- 13/100 +/- 7 mm Hg, p less than 0.001) and induced a significant rise in Na+ excretion (from 52 +/- 10 to 94 +/- 13 mmol/6 h) and in urine volume (from 520 +/- 80 to 947 +/- 120 ml/6 h; p less than 0.01). Sodium depletion significantly lowered supine blood pressure (152 +/- 12/95 +/- 9 mm Hg, p less than 0.001); nifedipine caused a further and significant blood pressure reduction (142 +/- 11/90 +/- 8 mm Hg, p less than 0.01), but only a minor and not significant increase in sodium excretion (from 10 +/- 2 to 22 +/- 5 mmol/6 h) and urine volume (from 338 +/- 76 to 463 +/- 94 ml/6 h). Our data suggest that the natriuretic action of calcium antagonists is not relevant to their antihypertensive effect.

Administration, Oral↗

Comparison of the antihypertensive effect of urapidil and metoprolol in hypertension.

The hypertensive effect of urapidil, a new antihypertensive agent that acts via central and peripheral alpha-adrenoceptors, has been compared with that of metoprolol in 40 patients with mild essential hypertension. Blood pressure was significantly reduced by both drugs, while the heart rate was reduced only after metoprolol. The increases in systolic blood pressure and heart rate caused by three progressive work loads of bicycle exercise were not affected during urapidil, whereas both were reduced by metoprolol. A slight reduction in forced expiratory volume was observed in some patients during treatment with the beta-blocker. There was no case of orthostatic hypotension during urapidil administration, despite its alpha1-blocking action. Side-effects were rare and negligible with both drugs.

Adult↗

The development of new antihypertensive drugs with specific properties for the treatment of established hypertension.

Despite the significant blood pressure reduction achieved in clinical studies of antihypertensive therapy, including the Medical Research Council studies, there has not been a significant reduction of coronary events. Different hypotheses have been proposed to explain the lack of cardioprotection seen in different trials, such as alterations of serum potassium and/or plasma lipids. Recent data indicate that patients with left ventricular hypertrophy at the start of pharmacologic treatment have a worse prognosis than patients with no electrocardiographic abnormalities. It is not known, however, whether the regression or persistence of left ventricular hypertrophy during antihypertensive treatment can influence the incidence of coronary events. According to present knowledge, indoramin, an alpha-adrenoceptor blocking drug, does not affect serum electrolyte and plasma lipid levels, which are among the characteristics to be evaluated in clinical trials designed to evaluate the possibility of better cardioprotection.

Antihypertensive Agents↗

Antihypertensive and renal effects of tertatolol, a new beta-blocking agent, in hypertensive patients.

Tertatolol, a new nonselective beta-adrenoceptor blocker, was administered to 11 hypertensive patients in a short-term study. Systolic and diastolic blood pressure and heart rate were significantly decreased when compared to the placebo period: in spite of that glomerular filtration rate and renal plasma flow were unchanged. The administration of metoclopramide (a dopaminergic receptor antagonist) caused a significant reduction of renal plasma flow and a significant rise of renal vascular resistances during placebo, but no change during tertatolol therapy. A possible interference of tertatolol on dopaminergic receptors is discussed as the mechanism responsible for the unmodified renal plasma flow despite the significant blood pressure lowering with tertatolol.

Adrenergic beta-Antagonists↗

Low-dose atenolol-chlorthalidone combination for treatment of mild hypertension.

In a randomized, double-blind, within-patient study, 28 out-patients with mild to moderate hypertension were given, at the end of a 3-week placebo wash-out period, four different antihypertensive treatments for 3 weeks each. the treatments were 50 mg atenolol, 100 mg atenolol, 12.5 mg chlorthalidone and a fixed combination of 50 mg atenolol and 12.5 mg chlorthalidone. All treatments were given once daily. Visits were scheduled for the last day of each treatment period, 24-26 hours after the last dose, and there was an intermediary wash-out period between each pair of active treatments. Supine systolic/diastolic blood pressure was 165/102 on placebo, 153/93 mmHg on 50 mg atenolol, 155/91 mmHg on 100 mg atenolol, 148/93 mmHg on 12.5 mg chlorthalidone and 144/89 mmHg on the combination. All the changes in pressure were significant (p less than 0.01) versus placebo. Supine systolic blood pressure was lower on the combination than on 100 mg atenolol alone (p less than 0.05) and upright systolic pressure was lower on the combination than on 100 mg atenolol (p less than 0.05) or 50 mg atenolol (p less than 0.05) alone. The heart rate was lowered by atenolol alone or combined with chlorthalidone but did not fall below 56 bpm in any patient. Serum potassium levels were lower on 12.5 mg chlorthalidone than on placebo (3.88 mEq/l vs 4.09 mEq/l--p less than 0.05) but the difference was trivial; on the combination of atenolol-chlorthalidone there was no significant difference versus placebo (3.97 mEq/l vs 4.09 mEq/l--NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗