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Biomedical subjects

G Leonetti

Publications and source records attributed to G Leonetti.

At least 163 records · Page 9Linked to original sources
PubMed1985

Natriuretic effect of calcium antagonists.

Calcium antagonists differ from traditional vasodilators by increasing renal water and sodium excretion, although the various calcium antagonist compounds influence renal excretory functions to a different extent. Two important aspects of the renal response to calcium antagonists are discussed, as they still need clarification: (a) the mechanisms of the diuretic and natriuretic effect; (b) the duration of this effect. Various mechanisms and sites of action can be envisaged to account for the diuretic and natriuretic action of these compounds. The action may be due to (a) a change in glomerular filtration rate and/or renal blood flow; (b) interference with renin release; (c) interference with aldosterone secretion and/or aldosterone action on distal tubule; (d) interference with adrenergic sodium handling; (e) a direct tubular action. Although the mechanisms may be multiple, the last type of action is likely to be the most important one. Recent balance studies of our group show that, although the diuretic and natriuretic actions of calcium antagonists are displayed acutely on the first or second day of administration, a negative sodium balance is maintained for at least 1 week, and the diuretic and natriuretic effects of these compounds are not overcome by water- and sodium-retaining mechanisms, unless the doses given are too large.

Aldosterone↗
PubMed1985

Antihypertensive and water and sodium balance effects of felodipine, a new vasodilating calcium antagonist, in hypertensive patients.

Felodipine, a new dihydropyridine derivative with a selective action on vascular smooth muscle, was investigated in 2 short term studies in hypertensive patients. In the first study, oral administration of felodipine 12.5 mg three times daily in a preliminary tablet formulation for 3 days significantly reduced supine and upright blood pressure with only a slight increase in heart rate and no clinically relevant signs of sodium and water retention. By increasing each dose to 25 and 50 mg three times daily, there was a further, but quite moderate, decrease in blood pressure; however, this was accompanied by an increase in heart rate and a tendency towards a reduction of creatinine clearance and urinary sodium output. In the second study, a new oral formulation containing 10 mg felodipine, administered twice daily for 7 days, was effective in lowering blood pressure without a clinically relevant tachycardia. Following the first dose of felodipine, urinary sodium excretion was slightly increased while potassium excretion showed only minor changes. The new calcium antagonist, felodipine, lowers blood pressure without the clinically relevant adverse reactions commonly related to other direct vasodilator antihypertensive drugs.

Adult↗
PubMed1985

Renal and antihypertensive effects of felodipine in hypertensive patients.

The effects of small doses of felodipine (10 mg twice daily) on blood pressure, renal function and sodium and water balance were studied in 11 patients with arterial hypertension. Felodipine significantly reduced systolic and diastolic blood pressure: most of the antihypertensive effect was already evident on day 1 of administration (-18/-11 mmHg) and only slightly increased during the subsequent week. Heart rate rose moderately only during day 1 of felodipine administration (+7 beats/min). Sodium excretion was increased during days 1 and 2, and no signs of water and electrolyte retention was observed in the week during which the balance study could be performed (Na, -135 +/- 65 mmol/7 days). At relatively low doses felodipine appears to be an effective antihypertensive agent, initially exerting some diuretic and natriuretic action and subsequently being devoid of a water- and sodium-retaining action.

Adult↗
PubMed1985

Renal effects of calcium antagonists in hypertensive patients.

This summary report of various clinical studies by our group describes the effects on renal excretion of water and sodium of several different calcium antagonists (verapamil, gallopamil, nifedipine and felodipine) which were administered for variable periods of time (from a single administration to repeated doses over up to 10 days) to hypertensive patients. All calcium antagonists tested displayed some diuretic and natriuretic action, despite profound differences in chemical nature and in pharmacodynamic properties. On single-dose administration the renal action of calcium antagonists was prompt, appearing during the first few hours, and decaying and ending after 6 h. When repeated doses were administered over several days the effect was at a maximum during the first 2 days and then disappeared in the following days, but the negative sodium balance which developed during the first 2 days was maintained for at least 7-10 days. The natriuretic effect was not accompanied by any change in the glomerular filtration rate, but with felodipine, a natriuretic effect observed at small doses reverted to an antinatriuretic effect at higher doses, at which the glomerular filtration rate was slightly decreased.

Calcium Channel Blockers↗
PubMed1985

Does beta 1-selective agonistic activity interfere with the antihypertensive efficacy of beta 1-selective blocking agents?

In order to investigate whether addition of beta 1-selective agonism can interfere with the antihypertensive efficacy of beta 1-selective adrenoceptor blockers, two separate studies were carried out to evaluate the effects on blood pressure and heart rate of three beta 1-selective blockers with or without varying degree of beta 1-selective agonism. In hypertensive patients at rest, the greatest blood pressure reduction and bradycardia were found with atenolol, a beta 1-selective blocker without any agonistic activity; a consistently smaller effect on blood pressure and heart rate was observed with Visacor (ICI 141 292), a beta 1-selective blocker with moderate beta 1-selective agonism, whereas no clinically relevant decrease in blood pressure occurred with Corwin (ICI 118 587), the beta 1-selective blocker with high beta 1-selective agonism. In contrast, during exercise-induced sympathetic activation, all three compounds reduced systolic blood pressure and heart rate to a similar degree.

Adrenergic beta-Agonists↗
PubMed1984

Verapamil and propranolol: a comparison of two antihypertensive agents.

Verapamil, a calcium antagonist, was compared with propranolol, a widely used beta-adrenoreceptor blocker, in hypertensive patients with respect to its antihypertensive efficacy and incidence and severity of adverse effects. Both drugs caused similar blood pressure reductions without interfering with pulse pressure. The hypotensive effect of verapamil was not accompanied by any effect on heart rate, while after propranolol there was a significant bradycardia. ST-segment and T wave abnormalities at rest and after exercise were partially or completely reverted by both drugs. The incidence and severity of adverse effects was very low and no patient was withdrawn from the study because of complaints due to the active drugs. Verapamil can be compared as antihypertensive drug to the beta-blocker propranolol and this may justify, together with the absence of negative effects on lipids, blood sugar, serum electrolytes and renal function, its use as an antihypertensive drug of first choice.

Adult↗
PubMed1983

Plasma catecholamines do not invariably reflect sympathetically induced changes in blood pressure in man.

Plasma concentrations of noradrenaline and adrenaline were measured radioenzymatically in nine subjects during 4 min pressor and depressor responses (intra-arterial measurements) induced by increasing and reducing sympathetic vasoconstrictor tone via carotid baroreceptor deactivation and stimulation (neck chamber technique). During the pressor response (15 +/- 3 mmHg, mean +/- SE) plasma noradrenaline and adrenaline showed various changes in the different subjects and on average were not significantly increased above control. During the depressor response (-9 +/- 2 mmHg) plasma noradrenaline and adrenaline also showed various changes in the subjects and were on average not significantly reduced below control. In contrast the same subjects all showed an increase in noradrenaline and adrenaline (average 76 and 117%) at the fourth minute of a tilting manoeuvre with a return to pretilting values no more than 4 min after resumption of the supine position. These results suggest that the moderate and/or restricted alterations in sympathetic tone produced by manipulating a single baroreflex, though capable of affecting blood pressure, are not reflected by alterations in plasma catecholamines. To modify these humoral indices significantly, the more drastic or more diffuse alterations in sympathetic activity that may be produced by manipulating low as well as high pressure reflexogenic areas are needed.

Adult↗
PubMed1982

Acute hypotensive and renin-stimulating actions of captopril before and during treatment with a beta-blocking drug.

There is no general agreement on the relation between the hypotensive effect of captopril and the pretreatment plasma renin levels of hypertensive patients. To determine whether the hypotensive effect of captopril was directly related to plasma renin, the angiotensin-converting enzyme inhibitor was administered acutely to 10 essential hypertensive patients with normal or suppressed plasma renin activity before and after inhibition of renin secretion with propranolol. Captopril was equally effective in reducing blood pressure both when administered alone (25 mg: -29/-17; 50 mg: -37/-23 mm Hg) and after chronic treatment with propranolol (25 mg: -33/-20; 50 mg: -30/-20 mm Hg). The increase in renin induced by captopril was not decreased by propranolol therapy. The persistence of the hypotensive effect of captopril after renin suppression by propranolol suggests that this drug has some blood pressure decreasing properties independent of plasma renin.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

Antihypertensive therapy in patients above age 60 with systolic hypertension. A progress report of the European Working Party on High Blood Pressure in the Elderly (EWPHE).

1. Although systolic blood pressure elevation is responsible for increased incidence of cardiovascular accidents in old people, the preventive benefit of lowering systolic hypertension in elderly has not been confirmed. 2. A double blind study comparing the effects of a placebo and of an active regimen (hydrochlorothiazide-triamterene with or without methyldopa) in people over 60 years with isolated systolic hypertension has been undertaken by the European Working Party on High blood pressure in the Elderly (EWPHE). 3. The actively treated group shows a lowered sitting blood pressure (-15/6 mm Hg), a mild increase of serum creatine, serum uric acid and blood glucose and a mild decrease of serum potassium after two years of treatment when compared to the spontaneous changes observed in the placebo treated group. 4. The study is continuing to evaluate if the blood pressure reduction prevents or reduces the incidence of cardiovascular accidents, although some biochemical changes were provoked by the treatment.

Aged↗
PubMed1982

Comparison of cardiovascular, renal, and humoral effects of acute administration of two calcium channel blockers in normotensive and hypertensive subjects.

The acute effects of two calcium channel blockers, nifedipine and verapamil, were compared in eight normotensive subjects and eight patients with essential hypertension. Nifedipine 10 mg and verapamil 160 mg orally had no effect on blood pressure of normal subjects, but reduced systolic and diastolic pressures of hypertensive patients to the same extent. The blood pressure reduction caused by nifedipine was more prompt and of lesser duration than that caused by verapamil. In both normal subjects and hypertensive patients nifedipine caused a transient rise in heart rate and plasma renin activity, and plasma catecholamines showed a tendency to increase; verapamil did not affect these variables. Nifedipine induced a marked increase in urine volume and renal sodium excretion in hypertensive patients, with a much smaller change in normotensives. Verapamil did not influence water and sodium excretion in either direction. Thus, this study shows similarities and differences between the effects induced by acute oral administration of the most-used vasodilating calcium antagonists.

Blood Pressure↗
PubMed1982

Influence of anti-hypertensive therapy on serum cholesterol in elderly hypertensive patients. Results of trial by the European Working Party on High blood pressure in the Elderly (EWPHE).

In the European Working Party trial on High blood pressure in the Elderly, patients over 60 are randomly allocated either to receive diuretic capsules containing 25 mg hydrochlorothiazide and 50 mg triamterene or matching placebos. If the blood pressure remains high those receiving active diuretic treatment also receive methyldopa. Those receiving a placebo diuretic area given placebo methyldopa tablets. The study is double blind, started in 1974 and is still in progress. Three hundred and thirty-one patients have now been followed for 1 year and of these 190 have been followed for 2 and 90 for 3 years. After 1 year the serum cholesterol in the placebo group fell by an average of 10.4 mg/100 ml; over 2 years the fall was 16.0 mg/100 ml and over 3 years 20.8 mg/100 ml (6.7%). The corresponding results for the actively treated group were falls of 3.1 mg/100 ml; 20.3 mg/100 ml and 17.3 mg/100 ml (6.6%). Over a period of up to 3 years the average fall in cholesterol was 5.9 mg/100 ml/year in the placebo group and 5.0 mg/100 ml/year in the actively treated group. Thus the changes in serum cholesterol were similar whether the patients received active or placebo medication. In particular there was no evidence for an increase in cholesterol nor for a smaller decrease during diuretic therapy. In the actively treated group the fall in blood pressure in the more hypertensive patients was accompanied by a fall both in haematocrit and serum cholesterol. In patients with less severe hypertension, active treatment was not accompanied by a fall in either hematocrit or cholesterol. These different responses of serum cholesterol in the more and less severe hypertensives in the present study could explain some of the previous conflicting reports on the influence of diuretic treatment on serum cholesterol.

Aged↗
PubMed1981

Carotid sinus reflex control of renin release in hypertensive subjects with high renin secretion.

1. Carotid baroreceptor manipulation (neck-chamber technique) and passive head-up tilting were used in ten patients with renovascular hypertension and in five subjects with essential hypertension under diuretic treatment to study reflex control of renin secretion at high basal-renin production rates. 2. Reflex effects of carotid baroreceptor manipulation on renin secretion were only minor. During baroreceptor deactivation there was a moderate increase in mean arterial pressure, but an inconsistent change in the renal venous--arterial difference in plasma renin activity (PRA). 3. During baroreceptor stimulation there was a modest fall in mean arterial pressure and a marked rise in the renal venous--arterial difference in PRA. This was opposite to the fall which might have been predicted as a result of the sympathetic depressor influence of the baroreceptor stimulus. Conversely, tilting increased the venous--arterial PRA difference by about 200%. 4. It is concluded that when renin production rate is high carotid baroreceptors exert little control over renin release, just as when renin production is low. Reflex control of renin, however, is very active in subjects with a high renin production, probably due to receptors in the cardiopulmonary region.

Adult↗
PubMed1980

Time-course of the anti-hypertensive action of atenolol: comparison of response to first dose and to maintained oral administration.

To show whether repeated administration of atenolol for several days would influence its pharmacokinetic parameters and the extent and duration of the pharmacologic responses, the plasma level of atenolol and changes in heart rate, blood pressure and plasma renin activity were measured in 12 hypertensive patients at various times of day (9 a. m., 12 noon, 3 p. m. and 7 p. m.) after oral administration of the first dose of atenolol 100 mg, again during the 7th and 14th days of continued once-daily administration of the same dose, and finally during the three days following withdrawal of the drug. The peak plasma concentration of atenolol (about 600 ng/ml) was found 3 h after administration of the first dose, and measurable amounts (50-70 ng/ml) were found after 24 h. None of the pharmacokinetic characteristics were changed by administration of a single daily dose for two weeks. After withdrawal of the drug, detectable amounts of atenolol were found in plasma for at least 48 h. The first dose of atenolol caused prompt (3 h) and prolonged (up to 24 h) lowering of supine and standing systolic and diastolic blood pressures, slowing of supine and standing heart rate, reduction of the blood pressure and heart rate responses to dynamic exercise, and a decrease in plasma renin activity. The extent and time-course of all these responses were not influenced by repeated once-daily administration of the 100 mg dose for two weeks. Most of the effects continued during the withdrawal days, the lowering of blood pressure being somewhat more prolonged than the slowing of heart rate. It is concluded that a once-daily dose of atenolol 100 mg decreases blood pressure and heart rate throughout the following 24 h, without excessive daily fluctuation in its effects, and without signs of tolerance or accumulation.

Administration, Oral↗