Acute renal tubular and hemodynamic effects of the calcium antagonist felodipine in healthy volunteers.

To evaluate the renal tubular effects of felodipine in a low (1.25-mg) and a high (10-mg) dose, lithium clearance was measured and related to renal hemodynamics in 10 healthy volunteers. After felodipine (1.

Effects of the calcium antagonist felodipine on the sympathetic and renin-angiotensin-aldosterone systems in essential hypertension.

Studies were performed in 10 male patients with untreated essential hypertension, WHO grade I-II, aged 25-62 years, to explore the acute (single dose) and long-term (8 weeks) effects of felodipine on sympathetic activity--evaluated by plasma and urinary catecholamines--as related to blood pressure, heart rate and the activity in the renin-angiotensin-aldosterone system. The patients were hospitalized for 8 (acute) and 6 (long-term) days and were maintained on a standardized daily intake of sodium (150 mmol), potassium (75 mmol) and water (2,500 ml). Acute felodipine administration (10 mg) significantly reduced blood pressure and increased heart rate.

Glucoregulatory hormone response to insulin-induced hypoglycaemia following long-term calcium antagonism with felodipine in patients with essential hypertension.

The effect of 8 weeks' treatment with the dihydropyridine calcium antagonist felodipine on glucoregulatory hormone response following insulin-induced hypoglycaemia was evaluated in 7 patients with essential hypertension, WHO grade I-II. After an iv insulin injection (0.1 IU/kg), blood glucose decrement and nadir were similar before and during felodipine treatment.

Catecholamines, renin-angiotensin-aldosterone, and cardiovascular response during exercise following acute and long-term calcium antagonism with felodipine in essential hypertension.

Studies were performed in nine patients with essential hypertension to explore the effect of the calcium antagonist felodipine on the exercise-induced responses of the sympathetic and renin-angiotensin-aldosterone systems as well as of blood pressure and heart rate. The patients were subjected to an individually graded submaximal work test (bicycling) after administration of placebo and a single dose of felodipine (10 mg) in a double-blind design and following long-term (8 weeks) felodipine treatment (10 mg twice daily). After a single dose of felodipine sitting preexercise blood pressure was decreased, whereas heart rate, plasma noradrenaline, adrenaline, renin activity, and angiotensin II increased.

Unchanged insulin secretion and glucose tolerance but increased insulin clearance during long-term calcium antagonism with felodipine in essential hypertension.

Studies were performed to explore the effect of calcium antagonism with felodipine for 8 weeks on glucose homeostasis and serum lipids in 8 patients with essential hypertension. Fasting levels of blood glucose as well as serum C-peptide, insulin, glucagon and free fatty acids were unchanged following felodipine. During an intravenous glucose tolerance test, the incremental area under the curve for C-peptide and glucose was unchanged, but decreased for insulin, after felodipine.

The influence of naloxone on exercise-induced increase in plasma pituitary hormones and the subjectively experienced level of exhaustion in healthy males.

Opioid peptides seem to play a role as modulators of the pituitary function in man. In the present study, the effect of naloxone on exercise-induced pituitary hormone release and the subjectively experienced level of exhaustion were investigated in nine healthy males. A submaximal work test was performed on two occasions using a bicycle ergometer: 10 min on 50% of maximal working capacity (MWC), immediately followed by 10 min on 80% of MWC.

Naloxone enhances the increase in plasma growth hormone induced by alpha 2-adrenergic stimulation in healthy males.

There is evidence that the alpha 2-adrenergic agonist clonidine interacts with the opioid system. In the present investigations, the effect of naloxone on the increase in plasma GH induced by clonidine and the more specific alpha 2-agonist guanfacine was studied in man. In a single-blind study, five healthy males received in randomized order either the preservatives in the naloxone preparation (control) or naloxone at two different doses (10 or 100 micrograms/kg) followed by an infusion of either diluted preservatives or naloxone (5 or 50 micrograms X kg-1 X h-1, respectively).

The effect of 8 weeks treatment with the calcium antagonist felodipine on blood pressure, heart rate, working capacity, plasma renin activity, plasma angiotensin II, urinary catecholamines and aldosterone in patients with essential hypertension.

The effect of 8 weeks treatment with the calcium antagonist felodipine--a new long-acting dihydropyridine derivative--in a dose of 10 mg twice daily was studied in 10 male patients with essential hypertension, WHO grade I-II, aged 25-62 years. Diastolic blood pressure was reduced in supine and upright position. Systolic blood pressure was reduced only in the upright position.

Alcohol withdrawal: effects of clonidine treatment on sympathetic activity, the renin-aldosterone system, and clinical symptoms.

Twenty male alcoholics with alcohol withdrawal syndrome were randomized to receive either oral clonidine (3-600 micrograms, six hourly) or oral chlormethiazole (500-1000 mg, six hourly) for 4 days. All subjects were also given oral carbamazepine (200 mg, 12 hourly) throughout the study. Nine subjects given clonidine and eight given chlormethiazole completed the study.

Lack of effect of naloxone in a moderate dosage on the exercise-induced increase in blood pressure, heart rate, plasma catecholamines, plasma renin activity and plasma aldosterone in healthy males.

There is evidence that opioid peptides influence blood pressure and heart rate in animals and man. In the present investigation the effect of naloxone on the exercise-induced increase in blood pressure, heart rate, plasma catecholamines, plasma renin activity (PRA) and plasma aldosterone was investigated in nine healthy men. A submaximal work test was performed on two occasions.

Partial blockade by naloxone of clonidine-induced increase in plasma growth hormone in hypertensive patients.

Studies in animals and man indicate a functional interaction between the adrenergic and the opiate systems. In the present study the effect of the opiate receptor blocker naloxone on the increase in plasma GH induced by clonidine was investigated in eight patients with essential hypertension. In a randomized order the patients received a bolus dose of naloxone (10 micrograms/kg) or physiological saline followed by a slow infusion of naloxone (5 micrograms/kg X h) or saline, respectively.

Failure of naloxone to reduce the clonidine induced reduction of blood pressure and plasma noradrenaline in patients with essential hypertension.

Studies in animals and man indicate a functional interaction between the adrenergic and the opiate systems. In the present study the effect of the opiate receptor blocker naloxone on the reduction of blood pressure and plasma noradrenaline induced by the alpha 2-agonist clonidine was investigated in nine patients with essential hypertension. In a randomised manner the patients received a bolus dose of naloxone (10 micrograms/kg) or physiological saline followed by a slow infusion of naloxone (5 micrograms/kg/h) or saline, respectively.

Effects of penbutolol and metoprolol on blood pressure, plasma catecholamines and renin activity in hypertensive patients.

The effects of penbutolol 20-30 mg twice daily and of metoprolol 50-150 mg three times daily were studied in five and nine patients, respectively, with moderate hypertension. Both drugs significantly reduced blood pressure and pulse rate under basal conditions and in connection with exercise. Plasma catecholamine levels were not altered in supine or upright position, neither during penbutolol nor during metoprolol treatment.

Plasma clonidine in relation to blood pressure, catecholamines, and renin activity during long-term treatment of hypertension.

Eight patients with essential hypertension were treated with 50 microgram oral clonidine four times daily for 4 wk followed by 75 to 150 microgram four times daily for another 4 to 16 wk. Before treatment and at the end of each treatment period the patients were hospitalized and their plasma clonidine concentrations (P-CLON) were determined repeatedly during one dosage interval. The relationship of P-CLON to blood pressure, heart rate, plasma norepinephrine (PNE), and plasma renin activity (PRA), as well as to conventional kinetic parameters, was calculated.

The effect of captopril on catecholamines, renin activity, angiotensin II and aldosterone in plasma during physical exercise in hypertensive patients.

The studies were designed to explore the effect of the converting enzyme inhibitor captopril on the activity of the sympathetic nervous system during basal conditions and following graded physical exercise in patients with essential hypertension. Seven males and two females, aged 36-59 years, were hospitalized under metabolic ward conditions and treated for 7 days with captopril given orally in increasing dosages, the final dose being 600 mg daily. The patients were subjected to an individual, graded submaximal work test (bicycling) for 20 min before medication and then again in an identical manner during medication with 600 mg captopril.

Plasma cyclic nucleotides and plasma catecholamines before and after prolonged treatment with clonidine in hypertensive patients.

The effect of standing and physical exercise and catecholamines and cyclic nucleotides in plasma was measured in 8 patients with essential hypertension under standardized conditions before and after prolonged treatment with clonidine. Before clonidine medication noradrenaline, adrenaline and cyclic AMP (cAMP) increased in response to standing and bicycling for 20 min. No significant correlation was found between their absolute levels nor was the increase in cAMP following exercise correlated to the increase in noradrenaline.

Kinins in relation to renin activity in renal and inferior caval veins in normal individuals and patients with primary aldosteronism.

Blood kinin concentration and plasma renin activity (PRA) were determined in the renal veins and in the inferior caval vein (ICV) below the level of the renal veins in 9 normal individuals (5 men and 4 women) and 7 patients with primary aldosteronism (3 men and 4 women). PRA in the renal veins and ICV was significantly lower and plasma aldosterone concentration in ICV significantly higher in the patients as compared to the normals. Kinin concentration in the renal veins and ICV did not differ significantly between the patients and the normals (0.

Pre- and postoperative studies in 72 hypertensive patients with renal artery stenosis, with special reference to renin activity and aldosterone.

Seventy-two patients, aged 6-69 years, were operated on because of presumed renovascular hypertension and subjected to follow-up studies for 4-60 months (mean 28). Unilateral renal artery stenosis was present in 47 patients. Surgery was followed by normalization of blood pressure (BP) in 28 and improvement in 7, whereas 12 showed no response.

Prolonged clonidine treatment: catecholamines, renin activity and aldosterone following exercise in hypertensives.

Eight patients with essential hypertension, WHO grade I-III, were studied under standardized conditions in a metabolic ward, before and after 8-20 weeks of treatment with clonidine in a maintenance dose of 300-600 micrograms/24 h. Before clonidine, plasma noradrenaline concentration (PNA), plasma adrenaline concentration (PA), plasma renin activity (PRA) and plasma aldosterone concentration (PAC) increased in response to standing and submaximal exercise for 20 min. PNA was positively correlated to pulse rate in the supine position (R = 0.