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Biomedical subjects

T Hedner

Publications and source records attributed to T Hedner.

At least 289 records · Page 16Linked to original sources
PubMed1987

Acute systemic and renal haemodynamic effects and long-term antihypertensive action of cadralazine in patients pretreated with beta-blockers and diuretics.

The antihypertensive effects of the hydralazine-related compound cadralazine (2-(3-[6-(2-hydroxypropyl)ethylamino]pyridazinyl)ethyl carbazate, ISF 2469), were investigated in 16 patients with primary hypertension concurrently treated with beta-blockers and diuretics. The protocol included a double-blind placebo controlled haemodynamic evaluation after the first tablet and two 4-week double-blind placebo controlled cross-over periods followed by an open evaluation during 2 months. Cadralazine induced a moderate, prolonged fall in blood pressure that was associated with vasodilatation and slight increases in cardiac output (dye-dilution) and heart rate. Renal plasma flow (PAH) and glomerular filtration rate (51Cr-EDTA) were not significantly influenced, but the filtration fraction was reduced. Plasma concentrations of noradrenaline and adrenaline rose, whereas plasma renin activity was unchanged. The haemodynamic parameters were not correlated with the plasma concentrations of cadralazine. During chronic cadralazine treatment the supine blood pressure was significantly lower than during the double-blind placebo phase (160/93 vs 174/102 mmHg). The compound was generally well tolerated but the body weight increased slightly (1.1 kg), probably because of fluid retention. Several patients who had previously experienced side effects with hydralazine, including one with hydralazine-syndrome, tolerated cadralazine well. This suggests that cadralazine does not cross-react with hydralazine.

Acute Disease↗
PubMed1987

Pharmacokinetics of ketanserin in patients with essential hypertension.

The pharmacokinetics of ketanserin and its main metabolite ketanserin-ol, and the antihypertensive effects of intravenous, single oral and chronic oral (40 mg once daily) administration of ketanserin, have been investigated in a single blind study of 10 patients with uncomplicated mild hypertension. Ketanserin had a terminal half-life of 29.2 h, a plasma clearance of 518 ml/min and a volume of distribution of 18.0 l/kg. Chronic oral intake of 40 mg ketanserin (tablet formulation) gave a peak concentration of unchanged ketanserin of 88 ng/ml after 1.1 h. Its absolute bioavailability was 48%. During chronic therapy the maximal concentration of ketanserin-ol was 208 ng/ml and its half-life of elimination was 35.0 h. As this metabolite can be oxidized back to ketanserin, it contributes to the prolonged half-life of unchanged ketanserin seen during chronic therapy. The blood pressure was reduced by approximately 15% by oral ketanserin. The maximal reduction in blood pressure coincided with the peak concentration of unchanged ketanserin. During chronic therapy with 40 mg once daily blood pressure was reduced over 24 h. The heart rate was slightly reduced and the cardiovascular responses and the plasma noradrenaline concentrations during isometric exercise were only slightly influenced by ketanserin therapy. Thus, unchanged ketanserin has a relatively long half-life during chronic oral therapy and its pharmacokinetics in middle-aged hypertensive patients is similar to that in normal young volunteers.

Administration, Oral↗
PubMed1987

Plasma atrial natriuretic peptide and blood pressure during chronic salt loading in spontaneously hypertensive rats with right atrial appendectomy.

Spontaneously hypertensive rats (SHR) were subjected to right atrial appendectomy (ATRX) or sham operated. Five days after this procedure the rats were put on tap water or 1.5% NaCl as drinking water for 1 week. The blood pressure (carotid artery), 24 hours urinary sodium and kalium excretion, plasma levels of immunoreactive atrial natriuretic peptide (ir-ANP) and the rise in plasma ir-ANP concentrations after an acute volume expansion by homologous whole blood (10%) were evaluated after 1 week on the different diets. At the start of the dietary period the rise in plasma ir-ANP values was blunted in ATRX rats. After 1 week the salt loaded animals excreted tenfold more sodium than control rats. At this time basal ir-ANP values in plasma were not significantly influenced by the ATRX and/or the high salt diet but the rise in plasma ir-ANP concentrations to acute volume expansion was blunted in the salt loaded rats. However, the basal blood pressure was not influenced by the salt diet and/or the ATRX. These data do not support the notion that an alleged deficiency in ANP release mechanisms in the SHR is a major determinant for the blood pressure development in this rat strain.

Animals↗
PubMed1987

Changes in plasma atrial natriuretic peptide--immunoreactivity in patients undergoing coronary artery bypass graft placements.

Plasma atrial natriuretic peptide immunoreactivity (IrANP) was measured before, during, and after cardiopulmonary bypass for coronary artery bypass graft placement. Eight subjects scheduled for elective operation had in the premedicated preoperative state slightly elevated IrANP compared to controls. Neither induction of anesthesia with a high dose narcotic/non-depolarising relaxant/diazepam technique nor cardiopulmonary bypass changed IrANP significantly. Mixed venous and arterial IrANP increased immediately after discontinuing bypass, and remained elevated 1 h later. Because ANPs affect peripheral resistance as well as urinary sodium loss, the post-bypass elevations in these peptides may contribute to cardiovascular and diuretic effects after cardiopulmonary bypass.

Anesthesia↗
PubMed1987

ANP--a cardiac hormone and a putative central neurotransmitter.

Isolation, purification and determination of the amino acid sequences of biologically active peptides were performed in 1983-84 by several groups. By that time the existence of such a humoral diuretic/natriuretic factor had been proposed for many years. The main, and perhaps the only, circulating form of atrial natriuretic peptide (ANP) is a 28 amino acid peptide structure with a disulphide bridge. This peptide is distributed mainly peripherally in the right and left cardiac atria. Smaller amounts are found in neonatal cardiac ventricles as well as in autonomic ganglia. In the central nervous system, high concentrations are found in hypothalamus, while lower concentrations are found in midbrain and brain stem regions. The amino acid sequence of ANP in the brain may be shorter than the form originating from cardiac atria. A 1 126 amino acid prohormone is present in granulae of atrial myocytes. After atrial distention the circulating 28 amino acid form is cleaved off. The main actions of this hormone include a diuretic/natriuretic effect, relaxation of vascular smooth muscle, and inhibition of basal or stimulated aldosterone secretion from the adrenal cortex. In the central nervous system, ANP has antidipsogenic actions, decreases salt appetite and lowers blood pressure. ANP may be of pathophysiological importance in several cardiovascular disorders such as congestive heart failure, paroxysmal supraventricular tachycardia and possibly also arterial hypertension. ANP seems to be a circulating hormone as well as putative neurotransmitter with important regulatory actions on salt and water homeostasis as well as blood pressure regulation.

Adrenal Cortex↗
PubMed1987

Antihypertensive effects and pharmacokinetics of felodipine combined with a beta-blocker and a diuretic.

The antihypertensive effect of felodipine, a new calcium antagonist with dihydropyridine structure, was investigated in 25 patients with essential hypertension that was not controlled on standard triple therapy (a beta-blocker, a diuretic, and a vasodilator). After substituting the previous vasodilator with felodipine, blood pressure was reduced and remained well controlled during a 2 year follow-up period. After about 1 1/2 years of treatment, felodipine was compared double-blind with placebo in a subgroup of 10 patients while keeping the same beta-blocker and diuretic therapy. Compared with the placebo, felodipine lowered blood pressure during a 12 h interval, which supports a twice-daily dosage in clinical practice. Determination of the plasma concentrations of felodipine during steady-state conditions showed a mean elimination half-life of 23.4 +/- 11.1 h. During long-term therapy, tolerance was good, and felodipine seems to be a safe and efficient antihypertensive agent in combination with a beta-blocker and a diuretic in patients whose hypertension is not adequately controlled on standard triple therapy.

Adrenergic beta-Antagonists↗
PubMed1987

Increased plasma levels of atrial natriuretic peptide (ANP) in patients with paroxysmal supraventricular tachyarrhythmias.

Atrial natriuretic peptide (ANP) is a cardiac hormone originating from atrial cardiocytes. It seems to be involved in the regulatory control of circulating volume and vascular tone. Plasma immunoreactive atrial natriuretic peptide (IrANP) was investigated in 22 patients with paroxysmal supraventricular tachyarrhythmia (16 with atrial fibrillation, 4 with atrial flutter, one with a Wolf-Parkinson-White syndrome (WPW) and one with atrial tachycardia). During the aute attack, IrANP was significantly increased (125.3 +/- 11.4 pmol/l) compared to samples obtained during convalescence (55.9 +/- 4.7 pmol/l). Heart rate (HR) was 144 +/- 4.3 beats/min during the arrhythmia and 75 +/- 2.6 during convalescence. The reduction of IrANP in plasma from the acute attack of tachycardia to follow-up was significantly related to the reduction of HR (p less than 0.05). Irrespective of type of paroxysmal supraventricular tachyarrhythmia, 50% of the patients experienced polyuria during the attack. This symptom was more frequent in younger patients with a shorter duration of tachycardia. Polyuria patients had a higher HR during the attack of supraventricular tachycardia. Even though polyuria was not always found in the patients with the highest IrANP values, the symptom was associated with significantly higher concentrations of IrANP in plasma compared to the non-polyuria group. We conclude that IrANP is increased in plasma during acute attacks of paroxysmal supraventricular tachycardia. Furthermore, the polyuria frequently associated with this condition may partly be due to excess release of ANP from cardiac myocytes.

Adult↗
PubMed1987

Significant relationship between renin suppression and atrial natriuretic peptide (alpha-hANP) during volume loading in hypertensive men.

We have studied eight men with moderate hypertension to determine the atrial natriuretic peptide (alpha-hANP) response to acute volume expansion. Rapid infusion of 1,000 ml 0.9% saline (10-20 min) caused an increase in central venous pressure (4.7 +/- 1.6 cmH2O) while blood pressure and pulse pressure (arterial baroreceptor load) did not change. Stroke volume and heart rate were not affected by the volume load but plasma renin activity (PRA) was significantly suppressed (from 0.83 +/- 0.14 to 0.68 +/- 0.34 microgram AI I/ml-h; p less than 0.01). A significant hemodilution was also observed. Renal sodium excretion was significantly increased. Arterial alpha-hANP increased significantly from 21.1 +/- 6.1 to 30.5 +/- 4.0 pmol/l (p less than 0.02) during volume expansion. There was a significant correlation between corrected plasma volume increase (urine volume subtracted from the infused volume) and alpha-hANP plasma elevation (r = 0.78; p less than 0.05). There was also a significant negative correlation between changes alpha-hANP and PRA (r = -0.78, p less than 0.05). We conclude that only moderate volume loading in human hypertensives is a mechanism for increase in plasma alpha-hANP levels. The significant negative correlation between changes in alpha-hANP and PRA suggests that alpha-hANP may be the humoral factor at least partly responsible for suppression of renin in hypertensive man. Since increased fluid volume also affects sympathetic renal efferents as well as vasopressin secretion, our observed relationship between volume load and renin may well be related also to such mechanisms.

Adult↗
PubMed1987

Water intoxication associated with non-steroidal anti-inflammatory drug therapy.

Two cases of rheumatoid arthritis, who developed severe hyponatremia after treatment with non-steroidal anti-inflammatory drugs (NSAID) are presented. Early diagnosis was followed by rapid correction with hypertonic saline. It is suggested that NSAIDs, like piroxicam, diclofenac and indomethacin, may be added to the list of drugs which can induce syndrome of inappropriate antidiuretic hormone (SIADH).

Aged↗
PubMed1987

Chronic 5-HT2-receptor blockade by ritanserin does not reduce blood pressure in patients with essential hypertension.

The selective 5-HT2-receptor-blocking agent ritanserin is an analogue of the antihypertensive agent ketanserin. By evaluating the antihypertensive effects of ritanserin the aim of this investigation was to indirectly elucidate the mechanism of action of ketanserin. Thirteen patients with essential hypertension were treated with placebo and ritanserin, 10 mg b.i.d., in a double-blind, cross-over design (4-week periods). At the end of the treatment periods blood pressure as well as plasma concentrations of ritanserin were evaluated for 24 hours. Despite high steady state and peak plasma concentrations of ritanserin the compound did not lower the blood pressure compared with placebo. Since chronic selective 5-HT2-receptor blockade by means of ritanserin did not lower the blood pressure, it is concluded that the 5-HT2 blocking properties of ketanserin cannot alone be responsible for the antihypertensive effects of ketanserin.

Aged↗
PubMed1987

Glucose tolerance in hypertensive patients during treatment with the calcium antagonist, felodipine.

1 Twelve non-diabetic hypertensive male patients insufficiently controlled by a diuretic were included in a double-blind, randomised study. In addition placebo or felodipine was given for 4 weeks followed by a 2 week wash-out period, after which the alternative treatment was given for another 4 weeks. At the end of each treatment period an oral glucose tolerance test (OGTT) was performed and blood pressure, plasma noradrenaline and felodipine levels were measured. 2 There was no change in either glucose, insulin or glucagon levels during the OGTT after felodipine compared with placebo. Blood pressure was significantly reduced during the dosage interval of felodipine (12 h). Plasma noradrenaline increased significantly after felodipine. Side effects were few. 3 In a separate open study 58 hypertensive patients were treated with felodipine in addition to a diuretic and a beta-adrenoceptor blocker for up to 1 year. There were no significant changes in fasting blood glucose levels during the study.

Blood Glucose↗
PubMed1987

Effects of chronic salt loading on plasma atrial natriuretic peptide (ANP) in the spontaneously hypertensive rat.

Plasma concentrations of immunoreactive atrial natriuretic peptide (ANP) was measured in spontaneously hypertensive rats (SHR) during chronic salt loading (1.5% NaCl in drinking water). During the 3-week experimental period mean arterial blood pressure, heart rate, urinary sodium excretion and body weight was assessed in salt-loaded as well as in control rats. The sodium excretion was more than 10-fold increased in the rats on the high salt diet. The plasma ANP concentration was significantly increased only 24 h after the start of the high salt intake. Thereafter plasma ANP concentrations were not significantly different from values obtained in control rats. The blood pressure was significantly increased after 3 weeks on the high salt diet. At the end of the 3-week experimental period the rats were subjected to a 10 and 20% acute volume expansion with homologous whole blood. During this intervention the increase in plasma ANP concentrations was blunted in the high salt rats compared to the control group. It is concluded that during chronic salt loading in SHR there is an initial rise in plasma ANP levels and that other hormonal and neuronal systems are more important in the long term maintenance of fluid and electrolyte balance.

Animals↗
PubMed1987

Respiratory stimulant effects by TRH into the mesencephalic region in the rat.

Thyrotropin-releasing hormone (TRH) has previously been found to have a potent respiratory stimulant effect following intracerebroventricular administration. One part of the respiratory response, the shortening of inspiratory time, seems to be elicited from the raphe obscurus in the medulla. The prominent tachypnoea however is not elicited after local injections in the medullary region. In the present paper a micro-injection technique was employed to study respiratory actions of TRH in lightly anaesthetized rats kept in a whole body plethysmograph. Thyrotropin-releasing hormone in a dose of 100 ng per 0.5 microliter was found to induce an immediate tachypnoea after injections into the region of the interpeduncular nucleus of the midbrain. No effects on systemic circulation were seen. More rostral or dorsal sites of injection were without effect. The localization of the sites responsible for respiratory stimulation corresponds to the reticular activating system where electrical stimulation induces hyperventilation in cats. The tachypnoea might be closely related to the well known arousal effects of TRH.

Animals↗
PubMed1987

Comparison of antihypertensive effect and pharmacokinetics of conventional and extended release felodipine tablets in patients with arterial hypertension.

In 2 separate double-blind, placebo-controlled, crossover studies, the antihypertensive effect and felodipine plasma concentrations were studied after 2 different formulations of felodipine. Both trials studied patients who had previously responded unsatisfactorily to conventional triple therapy (beta-adrenergic blocker, diuretic and vasodilator). Felodipine or corresponding placebo was added to the pre-existing beta-adrenergic blocker/diuretic combination. Both tablet formulations significantly lowered blood pressure. In patients taking plain felodipine tablets, 10mg bid for 10 days, the blood pressure reduction was evident for 12 hours but not 24 hours after each dose. At steady state, the maximal felodipine plasma concentration was 25.2 +/- 1.5 nmol/L and occurred 1.3 +/- 0.2 (range 1 to 3) hours after drug intake. When an extended release formulation of felodipine (20mg once every morning) was used, a more even plasma concentration curve was achieved. After 2 weeks' treatment, the maximal felodipine plasma concentration was 23.3 +/- 2.7 nmol/L and was reached 4.4 +/- 0.5 (range 3 to 7) hours after each dose. Systolic as well as diastolic blood pressure at steady state were reduced over 24 hours. No disturbing side effects were noted on either felodipine formulation. From these studies we conclude that oral felodipine lowers blood pressure in patients with moderate to severe hypertension when added to a beta-adrenergic blocker/diuretic combination. The extended release formulation given in a once-daily long term regimen produced a significant and equally satisfactorily controlled blood pressure reduction over 24 hours compared with the plain tablets but has the advantage of once-daily rather than twice-daily administration.

Antihypertensive Agents↗
PubMed1987

Felodipine in combination with a beta-blocker and a diuretic in chronic treatment of patients with refractory primary hypertension.

The acute antihypertensive effects of the dihydropyridine calcium antagonist, felodipine, were investigated in 12 male patients aged 43 to 64 years with uncontrolled blood pressure on combined treatment with a thiazide diuretic, a beta-blocker and hydralazine. Central and renal haemodynamics were monitored after acute oral administration (0.075 mg/kg) of felodipine in combination with the beta-blocker and diuretic. Six patients were continued on long term oral felodipine (mean dose 20 +/- 24 mg/day) in combination with the other drugs for 6 to 18 months. Ambulatory blood pressure was measured repeatedly and renal function re-examined once during long term felodipine therapy. In the 6 patients on long term therapy, systolic blood pressure was reduced from 190 +/- 17 to 149 +/- 24 mm Hg and diastolic blood pressure from 116 +/- 12 to 89 +/- 14mm Hg (p less than 0.001). No significant change in heart rate was observed (65 +/- 4 vs 62 +/- 10 beats/min). Renal plasma flow significantly increased from 284 +/- 97 to 425 +/- 131 ml/min/m2 (p less than 0.01) but glomerular filtration rate was unchanged (72 +/- 20 vs 80 +/- 22 ml/min/m2). Hence, the filtration fraction was significantly reduced and normalised in all patients (0.26 +/- 0.04 vs 0.20 +/- 0.03) [p less than 0.05]. Bodyweight was unchanged. It is concluded that felodipine is a highly potent vasodilator with a favourable effect on renal function and is suitable for long term therapy in patients with severe primary hypertension.

Adrenergic beta-Antagonists↗
PubMed1987

Opioids and opioid receptors in peripheral tissues.

Opioid peptides belonging to the enkephalin, beta-endorphin or dynorphin family, acting on specific opiate receptors may be found in peripheral tissues. Enkephalins have a widespread peripheral distribution, while beta-endorphin and dynorphin may be found locally in the enteric nervous system. The peptides of the various families are formed from specific precursor molecules. Apart from the enteric nervous system, opioids are also found in the adrenal medulla as well as in several autonomic ganglia. There is some evidence of three different classes of opioid receptors in peripheral tissues, i.e. mu-, delta- and kappa-receptors. These receptors are not only found on enteric nervous and mucosa cells but also on various cells in the immune system where opioid peptides seem to have important actions and appear to link the neuroendocrine and immune systems to control immunological functions. The physiological as well as the pathophysiological role of opioid peptides in the periphery is gradually being elucidated and, based on such knowledge, new therapeutic implications in gastrointestinal or immune diseases may be developed.

Animals↗
PubMed1987

Felodipine in hypertension--a review.

Felodipine lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels. The selective action may be considered a safeguard against untoward effects on cardiac contractility and conduction. Felodipine does not cause orthostatic hypotension since it has no effect in clinical doses on venous smooth muscle. Felodipine has a natriuretic/diuretic effect, which counteracts the salt and water retention that is often seen during treatment with other potent vasodilators. In clinical studies, felodipine has proved more effective than several established antihypertensive drugs. The combination of felodipine and a beta-adrenergic blocker appears to be a good alternative to standard triple treatment, and felodipine is often effective in patients with previously "refractory" hypertension. The antihypertensive effect of felodipine is dose related. In patients with moderate hypertension, a dose regimen of 5 mg twice a day is usually sufficient, and doses greater than 10 mg twice a day are not often required. Felodipine is generally well tolerated. The most common adverse effects are those expected from a potent arteriolar dilator: ankle swelling, headache, dizziness, flushing, etc. Adverse effects are usually transient or diminish in intensity with continued treatment. The overall frequency of adverse effects with felodipine appears to be similar to that for the established antihypertensive drugs, although the adverse effects differ. Felodipine is a potent arteriolar dilator with therapeutic advantages, especially for patients with moderate to severe hypertension.

Blood Pressure↗