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Biomedical subjects

T Hedner

Publications and source records attributed to T Hedner.

At least 181 records · Page 10Linked to original sources
PubMed1994

The effects of alpha-trinositol on haemodynamic variables and neuropeptide Y levels in a pilot study of hypertensives and healthy volunteers.

AIMS: The aim of this study was to examine the effects of D-myo-inositol-1,2,6-trisphosphate (alpha-trinositol) on haemodynamic variables and neuropeptide Y (NPY) levels in hypertensives and healthy volunteers. METHODS: Hypertensives (n = 13) and normotensives (n = 11) were recruited after a screening of cardiovascular risk factors of all men aged 40 living in a well defined area. The hypertensives were previously unmedicated. The effect of alpha-trinositol was studied after intravenous infusion at rest, and during and after a maximal exercise test in a double-blind crossover manner with placebo. RESULTS: Haemodynamic variables and NPY levels were recorded. NPY levels did not differ between normotensives and mild hypertensives at the start of the study. However, a significant increase was seen in hypertensives after they had risen to the sitting position. During exercise, the NPY levels increased significantly both in normotensives and hypertensives. After the exercise test, the NPY levels were significantly higher in hypertensives than in normotensives; alpha-trinositol did not modify these responses. In normotensives no significant difference in systolic blood pressure was seen during or after the exercise test whether they were on alpha-trinositol or placebo. In the hypertensives on active drug, however, the blood pressure tended to be approximately 5 mmHg lower during the exercise test as compared with the placebo group. In the hypertensives on active drug, the heart rate increased significantly more during exercise as compared with the placebo groups. In normotensives, the same tendency was seen, but it did not reach statistical significance. CONCLUSIONS: The NPY antagonist, alpha-trinositol, tends to reduce the increase in systolic blood pressure induced by maximal exercise and increases the heart rate in hypertensives but not in normotensives.

Adult↗
PubMed1994

Diabetes mellitus in treated hypertension: incidence, predictive factors and the impact of non-selective beta-blockers and thiazide diuretics during 15 years treatment of middle-aged hypertensive men in the Primary Prevention Trial Göteborg, Sweden.

The objective of this study was to analyse predictive factors for the development of diabetes mellitus during long-term treatment of hypertension and to compare the diabetogenic potential of thiazide diuretics and non-selective beta-adrenoceptor blockers. The study population comprised 686 hypertensive men, aged 47-54 years, who were followed for 15 years. Patients were treated with either thiazide diuretics or beta-adrenoceptor blockers as monotherapy or in combination with one another or alternative other antihypertensive drugs. During the first part of the study, i.e. during the 1970s, only non-selective beta-adrenoceptor blockers were used. The average yearly incidence of the development of diabetes mellitus during follow-up was 1.3%. In univariate analysis body mass index, serum triglyceride level, radiographic heart enlargement and beta-blocker therapy were significantly associated with the development of diabetes mellitus. Predictors selected by stepwise Cox regression were body mass index, radiological heart enlargement and beta-blocker therapy. Two subgroups with patients treated with nonselective beta-adrenoceptor blockers but not with thiazide diuretics during the first five years of follow-up (the beta-blocker group; n = 93) or with thiazide diuretics but not with nonselective beta-adrenoceptor blockers during the first five years of follow-up (the thiazide-group; n = 96) were identified. The relative risk for developing diabetes mellitus was significantly higher in the beta-blocker group being 6.1 after 10 years and 3.5 after 15 years treatment in comparison with the thiazide group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1993

Serotonin-induced platelet aggregation predicts the antihypertensive response to serotonin receptor antagonists.

The 5-HT2-receptor antagonist ketanserin (20-40 mg b.i.d.) was administered to 62 patients of both sexes with uncomplicated primary hypertension. After 4 weeks of treatment about 50% of the patients had reached the target diastolic blood pressure of 90 mm Hg or below. Interindividual variability was large. In a retrospective analysis the variability could not be explained by sex or the dose of ketanserin. There was a weak association between age and systolic blood pressure response (r = 0.24; P = 0.06), which could be entirely accounted for by the higher base line blood pressure in the elderly patients. In one group of patients (n = 12), the ex vivo aggregation to serotonin (10(-6) M) was studied during treatment with placebo and ketanserin. Ketanserin completely inhibited 5-HT-induced aggregation in all patients. There was a close correlation between the area under the 5-HT-induced platelet aggregation curve during placebo and the subsequent reduction in diastolic blood pressure after 4 weeks of treatment with ketanserin. The present data suggest that the blood pressure response to ketanserin can be predicted from the ex vivo sensitivity of platelets to serotonin. By implication, they also support a role for serotonergic mechanisms in hypertension.

Adenosine Diphosphate↗
PubMed1993

Sympathetic activation after two weeks of nifedipine treatment in primary Raynaud's patients and controls.

The effect of a standardized cold pressor test on circulating noradrenaline and neuropeptide-Y-like immunoreactivity was investigated in 12 women with primary Raynaud's phenomenon and 12 healthy female controls before and after 2 weeks of treatment with the calcium antagonist, nifedipine. Measurement before treatment showed significant increase during the cold pressor test on circulating noradrenaline in both the primary Raynaud's phenomenon group and in the control group (from 0.29 +/- 0.15 ng/ml to 0.33 +/- 0.16 ng/ml, p < 0.05, and from 0.21 +/- 0.14 ng/ml to 0.29 +/- 0.16 ng/ml, p < 0.005, respectively). However, treatment with nifedipine resulted in significantly increased levels of circulating noradrenaline during the cold pressor test only in the control group (from 0.43 +/- 0.21 ng/ml to 0.50 +/- 0.20 ng/ml, p < 0.01). Plasma concentrations of neuropeptide-Y-like immunoreactivity were unchanged by the standardized cold pressor test, whether performed before or during nifedipine treatment in both groups. Nifedipine treatment per se significantly increased circulating noradrenaline in both the primary Raynaud's phenomenon patient group and in the control group (from 0.29 +/- 0.15 to 0.49 +/- 0.13 and 0.21 +/- 0.14 to 0.43 +/- 0.21 ng/ml, respectively, p < 0.001). Similarly, the circulating neuropeptide-Y-like immunoreactivity significantly increased in both the primary Raynaud's phenomenon group and in the control group (from 105 +/- 21 to 137 +/- 19 pmol/l and 107 +/- 17 to 147 +/- 13 pmol/l, respectively, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Pharmacokinetic evaluation of oral 17 beta-oestradiol and two different fat soluble analogues in ovariectomized women.

A randomised, single-blind comparative study was carried out in 9 ovariectomized women to evaluate the kinetics of single doses of three different steroid combinations: 0.150 mg desogestrel + 2.0 mg micronized 17 beta-oestradiol, 0.150 mg desogestrel + 0.500 mg 17 beta-oestradiol cyclo-octyl acetate and 0.150 mg desogestrel + 1.0 mg 17 beta-oestradiol decanoate. Serum levels of 17 beta-oestradiol and oestrone were measured, as well as the excretion of 17 beta-oestradiol and its metabolites (oestrone and oestriol) in urine. In relation to the doses given, higher peak serum concentrations of 17 beta-oestradiol were obtained after the two fat soluble analogues, while the AUCs were similar to that after micronised 17 beta-oestradiol. However, there was more extensive conversion of the micronised 17 beta-oestradiol preparation into oestrone compared to 17 beta-oestradiol cyclo-octyl acetate and 17 beta-oestradiol decanoate. The oestrone/17 beta-oestradiol serum concentration ratio was approximately 2.6 before tablet intake and remained essentially unchanged after intake of 17 beta-oestradiol cyclo-octyl acetate and 17 beta-oestradiol decanoate. After micronized 17 beta-oestradiol however, there was a 2-3-fold increase in the ratio at Cmax and slower elimination of 17 beta-oestradiol from plasma, which may be due to the fact that high serum oestrone levels may serve as a reservoir, since both a metabolite and also a precursor of 17 beta-oestradiol. The urinary excretion of 17 beta-oestradiol, oestrone and oestriol was highest after oral administration of micronized 17 beta-oestradiol compared to 17 beta-oestradiol cyclo-octyl acetate and 17 beta-oestradiol decanoate.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Benzodiazepine amplification of valproate teratogenic effects in children of mothers with absence epilepsy.

Valproate (VPA) is one of the most frequently used antiepileptic drugs (AEDs). Concern has recently been raised regarding VPA medication during pregnancy and teratogenic effects in the offspring. Both neural tube defects (5, 18, 34) and a constellation of signs termed the fetal valproate syndrome (1, 12) have been reported. Benzodiazepines (BZDs) are also widely used and sometimes as effective adjunctives in AED therapy. Both VPA and BZD have close connections to GABA transmission. Recently, clinical and epidemiological human studies (26, 27, 37, 39), supported by animal studies (17, 24, 40), have indicated that BZDs may act as human teratogens. We report on 7 children with congenital malformations, dysmorphism and abnormal neurological signs from birth. The mothers had well controlled primary generalized absence epilepsy without major seizures during pregnancy. Five children had been exposed to VPA monotherapy and two children to VPA and BZD combined during the first trimester. Those two infants had myelomeningoceles and the most pronounced dysmorphism in the group. We propose that these observations indicate a possible amplifying action of BZDs on VPA teratogenicity. Unrecognized BZD use during pregnancies exposed to VPA may be of importance when estimating the teratogenic risks of VPA therapy.

Abnormalities, Drug-Induced↗
PubMed1993

Hypersensitivity of Gi protein mediated muscarinic receptor adenylyl cyclase in chronic ischaemic heart failure in the rat.

OBJECTIVE: The aim was to study the Gi protein mediated muscarinic signalling system in the myocardium of rats with chronic ischaemic heart failure. METHODS: Chronic ischaemic heart failure was induced by myocardial ischaemia (four weeks after coronary artery ligation) in rats. The densities and agonist affinities of muscarinic receptors, and the functional activity and concentration of Gi proteins were studied. RESULTS: In failing hearts, the activity of adenylyl cyclase stimulated by guanyliminodiphosphate (Gpp(NH)p) was decreased by 46%. Stimulated activities of adenylyl cyclase by both sodium fluoride and forskolin, however, remained unchanged. Carbachol depressed forskolin stimulated adenylyl cyclase more in membranes from failing hearts than those from normal hearts. The functional level of Gs protein as measured by a reconstitution assay in sarcolemmal membrane did not differ between the two groups. Furthermore, muscarinic receptors exhibited superhigh and low affinities for agonist in failing hearts whereas those in control hearts displayed only high and low affinities. No significant difference in the peptide equivalent amount of membrane bound Gi protein was found in either group. CONCLUSIONS: The experimental chronic failing heart due to myocardial ischaemia showed a depressed myocardial adenylyl cyclase signalling system. This may be due to the hypersensitivity of the Gi protein mediated muscarinic receptor-adenylyl cyclase system as shown by the increased inhibition of Gpp(NH)p mediated adenylyl cyclase, more potent inhibition of stimulated adenylyl cyclase by carbachol, and the superhigh affinity of the muscarinic receptors for carbachol.

Adenylyl Cyclases↗
PubMed1993

Atrial peptides, ANP(1-98) and ANP(99-126) in health and disease in an elderly population.

Circulating immunoreactive atrial natriuretic peptide, IrANP(99-126) and the N-terminal fragment of the prohormone, IrANP(1-98) were measured in two population samples from the general population of Gothenburg, Sweden. A group of 85-year olds (974 subjects) and a group of 40-year olds (191 subjects) were investigated in respect of cardiovascular, renal and metabolic disease. IrANP(99-126) and IrANP(1-98) were significantly higher in the 85-year olds compared to the 40-year olds, and were significantly increased in subjects with congestive heart failure, ischaemic heart disease, atrial fibrillation and renal dysfunction but not in subjects with hypertension. Eighty-five-year-old subjects who were on treatment with digitalis, beta-adrenergic-blockers, nitrates and diuretics had significantly increased IrANP(99-126) and IrANP(1-98). In multivariate analysis IrANP(99-126) concentrations were predictive for congestive heart failure, ischaemic heart disease, atrial fibrillation and treatment with beta-blockers and anti-depressant drugs. IrANP(1-98) was predictive for congestive heart failure, ischaemic heart disease, atrial fibrillation, diabetes mellitus, renal failure and drug treatment with beta-blockers and neuroleptics. We conclude that measurements of circulating concentrations of IrANP(99-126) and/or IrANP(1-98) may add valuable information in the diagnosis of congestive heart failure and ischaemic heart disease in an elderly population. It remains to be determined whether routine measurements of circulating IrANP (99-126) and IrANP(1-98) may be of value in predicting current cardiovascular disease for the individual patient.

Adult↗
PubMed1993

Cardiovascular effects of alpha-trinositol in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

OBJECTIVE: To investigate the cardiovascular effect of alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate; PP56) in spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto (WKY) rats. alpha-Trinositol, a representative of a new group of pharmacological agents, is an inositol phosphate which seems to bind to a single population of binding sites, inhibiting, for example, agonist-induced vasoconstriction. In particular, alpha-trinositol seems to inhibit agonist-induced (e.g. neuropeptide Y-induced) elevations in intracellular Ca2+ levels in vascular smooth muscle cells. METHODS: alpha-Trinositol was administered as a bolus injection (2-40 mg/kg body weight), followed by a continuous infusion (20-400 mg/kg body weight per h) for 40 min in freely moving SHR and WKY rats. RESULTS: Acute intravenous bolus administration of alpha-trinositol reduced systolic and diastolic blood pressure, as well as heart rate, in a dose-dependent manner in SHR and WKY rats. After completion of the 40-min infusion the reduction in blood pressure was more pronounced in the SHR than in the WKY control rats. Heart rate did not change in the SHR, whereas it was significantly increased at the highest dosage (400 mg/kg) in the WKY rats. At this dosage, three out of eight SHR died from cardiac arrhythmias after completing the infusion. The lowest dose of alpha-trinositol administered (2 mg/kg bolus followed by 20 mg/kg per h infusion over 40 min) significantly inhibited the increase in mean arterial pressure induced by neuropeptide Y (2 micrograms/kg per min for 10 min) by approximately 30% in both the SHR and WKY rats. Furthermore, alpha-trinositol treatment completely inhibited the potentiation induced by neuropeptide Y (0.1 micrograms/min for 30 min) of the blood pressure responses to intravenous bolus injections of noradrenaline (20 ng), tyramine (40 micrograms) or angiotensin II (10 ng). CONCLUSIONS: Our results demonstrate that alpha-trinositol antagonizes the direct postsynaptic pressor response to exogenous neuropeptide Y, as well as the potentiating effects of neuropeptide Y on other vasoconstrictors in SHR and WKY rats. However, in the SHR alpha-trinositol lowered basal blood pressure only in the dose range which was non-specific for neuropeptide Y inhibition. Thus, the present study indicates that neuropeptide Y is involved only slightly in the maintenance of high blood pressure in SHR.

Animals↗
PubMed1993

Decreased density of mesenteric arteries but not of myocardial endothelin receptors and function in rats with chronic ischemic heart failure.

Mesenteric artery and cardiac ventricular endothelin receptors and endothelin-1-induced pressor responses were studied in normal rats and rats with chronic congestive heart failure induced by myocardial ischemia (4 weeks after coronary artery ligation). In mesenteric arteries of rats with chronic ischemic heart failure, endothelin receptor density was significantly decreased by 59%, whereas the dissociation constant was increased 2.8-fold, as compared with controls. There were, however, no changes in endothelin-receptor density or the dissociation constant in cardiac ventricular membrane preparations from rats with congestive heart failure as compared with controls. In pithed rats with congestive heart failure there was a reduced pressor response to a bolus injection of endothelin-1 (800 pmole/kg body weight), while the vasodilatory response was unaltered as compared with sham-operated controls. These results demonstrate that there is a decreased vascular endothelin-receptor function due to a down-regulated endothelin receptor. The in vivo data indicate that this is due to impaired endothelin A but not endothelin B receptor function. Thus, there is an impaired arterial but not cardiac ventricular endothelin receptor-mediated signalling system in the rat with chronic ischemic heart failure.

5'-Nucleotidase↗
PubMed1993

Effect of coffee on ambulatory blood pressure in patients with treated hypertension.

Effects of caffeine on ambulatory blood pressure, heart rate, renin-angiotensin system, and ANP were studied in patients treated for mild to moderate hypertension in a randomized, double-blind, placebo-controlled, cross-over trial comparing 2 weeks of caffeine-free diet with 2 weeks of regular coffee use. Twenty-three patients (13 men; aged 28-74 years) with treated, mild to moderate essential hypertension and a regular intake of 3-4 cups of coffee daily completed the study. Mean 24-h, day- or night-time ambulatory blood pressure and heart rate were not different between regimens. Nor were there any effects on the renin-angiotensin system while ANP was significantly increased during caffeine intake. Compliance of the dietary regimen was excellent as assessed by serum caffeine concentration measurements. We conclude that habitual coffee drinking did not influence the 24-h blood pressure profiles or cardiovascular hormones in treated hypertensives.

Adult↗
PubMed1993

CSF neuropeptides in cancer pain: effects of spinal opioid therapy.

The cerebrospinal fluid (CSF) levels of the opioid peptides met-enkephalin (ME), beta-endorphin (BE) and dynorphin (DYN) as well as the putative sensory neuropeptides substance P (SP), somatostatin (SOM), calcitonin gene related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were determined in 10 patients with severe nociceptive pain due to malignancy, before and after initiation of spinal opioid therapy, and in 10 control patients. Pain intensity, evaluated by means of a 100-mm visual analog scale (VAS), was reduced from 39 +/- 9 to 18 +/- 10 for continuous pain and from 70 +/- 10 to 10 +/- 8 for intermittent pain (means +/- s.e.mean). Lumbar CSF immunoreactive ME and DYN concentrations were significantly increased (P = 0.05) and BE and VIP were significantly decreased (P < or = 0.05) in the pain patients. A slight, but non-significant (P = 0.06) decrease in SP-like immunoreactivity was found after initiation of spinal opioid therapy. Visceral pain seemed to be associated with low immunoreactive SP and ME concentrations compared to somatic pain. A highly significant correlation was found between SP and ME (P < 0.001) and to a lesser extent also between other peptides. We conclude that the concentrations of the endogenous opioids were more affected by nociceptive pain states than the non-opioid peptides. The origin of pain may also influence the results. The postulated inhibition of peptide release by spinal opioid application seemed to be present for SP, but could otherwise not be confirmed.

Aged↗
PubMed1993

Effects of cold pressor test on circulating atrial natriuretic peptide 99-126 (ANP) in patients with Raynaud's phenomenon and influence of treatment with magnesium sulphate and nifedipine.

The effect of a standardized cold pressure test (CPT) on the venous concentration of immunoreactive atrial natriuretic peptide (irANP) was studied in 12 females with primary Raynaud's phenomenon (PRP) and 12 female age-matched controls. The test was performed at the end of three stages. During the first stage no medication was given. During the second stage a magnesium infusion was given. After fourteen days of medication with a calcium antagonist (Nifedipine) the third stage of the study was performed. The venous irANP increased significantly (P < 0.05) 10 min after the start of the CPT both in the PRP group and in the control group (136 +/- 39 to 159 +/- 54 and 153 +/- 45 to 179 +/- 40 pg ml-1, given as mean and SD). Baseline irANP did not change in the PRP group after treatment with magnesium or nifedipine. In the control group nifedipine treatment significantly (P < 0.01) lowered venous irANP compared to the no treatment or magnesium sulphate infusion stages (128 +/- 31 vs. 153 +/- 45 and 160 +/- 41 pg ml-1). After the CPT in both PRP group and control group the venous irANP did not increase either during magnesium sulphate infusion or nifedipine treatment. In conclusion the study has demonstrated that a standardized CPT results in a delayed increase in irANP in venous plasma and that magnesium sulphate infusion and nifedipine treatment prevent this increase. Furthermore, our data do not suggest a role for irANP in the symptomatology of primary Raynaud's phenomenon.

Adult↗
PubMed1993

STOP-Hypertension 2: a prospective intervention trial of "newer" versus "older" treatment alternatives in old patients with hypertension. Swedish Trial in Old Patients with Hypertension.

It is well established that hypertensive patients benefit from drug treatment of their disorder. In recent years three major out-come studies of antihypertensive treatment in elderly hypertensives have shown substantial benefits, i.e. a reduction in the risk of stroke and other cardiovascular mortality and morbidity. In all these studies beta-blockers and/or diuretics were used in comparison with placebo. Newer therapeutic alternatives have, however, at least theoretically, many advantages which could result in further improvements in prognosis. The initial Swedish Trial in Old Patients with Hypertension (STOP-Hypertension 1) was conducted in men and women aged 70-84 years. STOP-Hypertension 2 will evaluate the therapy used in STOP-Hypertension 1 against therapy based on either ACE-inhibitors (enalapril and lisinopril) or on calcium antagonists (isradipine and felodipine), using the PROBE design (Prospective, Randomised, Open, Blinded Endpoint evaluation). The primary aim will be to assess the effect on cardiovascular mortality. Statistical calculations indicate that 6,600 patients, followed for four years will be needed (2p < 0.05, power 90%) to obtain significance if there is a 25% difference between the new and the established therapy. Patients in primary health care (300 centres) will be included if their supine blood pressure is > or = 180/105 mmHg (and/or). Recruitment of patients started in September 1992 and so far more than 100 patients/week have been included.

Aged↗