Break-through for calcium antagonists in the treatment of hypertension based on the Syst-Eur results.
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Calcium Channel Blockers↗
Biomedical subjects
T Hedner
Publications and source records attributed to T Hedner.
Increased circulating concentrations of asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, in preeclampsia.
OBJECTIVES: To study endogenous nitric oxide (NO) synthesis inhibitors in preeclampsia by measuring asymmetric dimethyl arginine (ADMA) and arginine. STUDY DESIGN: Blood samples for measurement of plasma concentrations of ADMA and arginine were obtained antepartum (range 32-39 weeks gestation), 3-5 days postpartum and 3 months postpartum from 12 pregnant women with severe preeclampsia and from a normotensive pregnant control group (n=12). RESULTS: During the third trimester, plasma ADMA was elevated (p<0.05) in the preeclampsia patients (0.55+/-0.02 micromol/l) compared to the normotensive pregnant controls (0.36+/-0.01 micromol/l). Since plasma arginine levels did not differ between preeclamptic and normotensive control women (80.7+/-5.8 micromol/l) and 74.5+/-3.8 micromol/l respectively), the plasma arginine/ADMA ratio was lower (p<0.05) in the preeclamptic group (145.6+/-10.5) compared to the normotensive controls (211.0+/-14.3). Three days post partum there was an increase (p<0.05) in plasma ADMA in both the preeclamptic (0.67+/-0.03 micromol/l) and the normotensive control group (0.64+/-0.03 micromol/l). This was accompanied by a rise (p<0.05) in plasma arginine levels in both the preeclamptic patients (112.9+/-10.5 micromol/l) and the normotensive control group (121.7+/-9.6 micromol/l). At this time point there was no difference in plasma arginine/ADMA ratio between the groups. Three months postpartum, plasma ADMA levels were slightly lower in both groups compared to the postpartum values (preeclampsia: 0.56+/-0.03 micromol/l, normotensive pregnant control: 0.52+/-0.03 micromol/l). CONCLUSION: Elevated circulating ADMA concentrations in combination with low plasma arginine levels may be of pathophysiological importance in pregnancies complicated with preeclampsia.
Arginine↗
Endothelin may be pathogenic in systemic sclerosis of the heart.
We evaluated 30 consecutive patients and 48 age- and sex-matched controls to explore the possibility of a pathogenic contribution by plasma endothelin-1 in the cardiac expression of systemic sclerosis. Venous plasma endothelin-1 was measured by radio-immunoassay and left ventricular function by echocardiography. The patient group had elevated plasma endothelin-1 (2.6 +/- 0.2 vs. 1.8 +/- 0.1 pmol/1, P < 0.001), but endothelin-1 was not related to age, heart rate, blood pressure, total peripheral resistance, disease duration or systemic sclerosis score. Endothelin-1 was related to left ventricular hypertrophy in terms of septal thickness (r = 0.33, P < 0.01) and left ventricular mass index (r = 0.32, P < 0.01). Plasma endothelin-1 was further related to measures indicating reduced left ventricular filling; left atrial emptying index (r = -0.50, P < 0.0005), the first third filling fraction (r = -0.31, P < 0.05) and the time velocity integral of Doppler early/late filling velocity (r = -0.40, P < 0.001). Furthermore, circulating endothelin-1 was related to impaired left ventricular contractility as estimated by pre-ejection period/left ventricular ejection time (r = 0.32, P < 0.01) and end-systolic wall stress/volume index (r = -0.30, P < 0.05). We conclude that plasma endothelin-1 is elevated in relation to the degree of left ventricular hypertrophy, diastolic dysfunction and impaired contractility in systemic sclerosis. It may be of pathogenic importance to the cardiac involvement in systemic sclerosis which is not mediated via an increase in systemic blood pressure. It is not yet clear whether our findings are exclusive to systemic sclerosis patients or represent a generalized phenomenon in patients with impaired left ventricular function.
Adult↗
The effect of alpha-trinositol (D-myo-inositol 1,2,6-trisphosphate) on formalin-evoked spinal amino acid and prostaglandin E2 levels.
The effect of the inositol trisphosphate analog alpha-trinositol on noxious-evoked behavior, amino acid and prostaglandin E2 (PGE2) release was examined in unanesthetized rats using intrathecal microdialysis probes. Subcutaneous injection of 50 microliters 5% formalin solution produced two phases of pain-like behavior and significant elevation of glutamate, aspartate, glycine, taurine and serine during phase 1. PGE2 concentrations were increased during both phases 1 and 2. Intraperitoneal delivery of 300 mg/kg alpha-trinositol significantly suppressed both phases 1 and 2 of formalin-induced behavior and the associated elevation of amino acids and PGE2. These data demonstrate that the antinociceptive effect of alpha-trinositol corresponds to suppression of noxious-evoked release of amino acids and PGE2 from the spinal cord.
Amino Acids↗
Effects and pharmacokinetics of high dose metoprolol on chest pain in patients with suspected or definite acute myocardial infarction.
OBJECTIVE: Pain intensity and the plasma concentrations of metoprolol and its major metabolite alpha-hydroxymetoprolol as well as noradrenaline (NA), adrenaline (A) and neuropeptide Y (NPY) were determined in patients with pain due to definite or suspected acute myocardial infarction (AMI) after graded metoprolol infusion. Pain intensity and metoprolol kinetics were assessed over 8 h. METHODS: Twenty-seven patients of either sex, aged 48-84 years with ongoing chest pain upon arrival to the Coronary Care Unit (CCU) were subdivided into two groups: (1) patients with ECG signs of threatening transmural myocardial damage (n = 15); and (2) patients without such ECG signs (n = 12). Pain intensity was assessed by a numerical rating scale (NRS) and venous blood was obtained for determination of plasma catecholamine and NPY concentrations. A continuous infusion of metoprolol (3 mg.min-1 i.v) was started and serial blood samples for plasma catecholamines, NPY as well as metoprolol and its major metabolite alpha-hydroxymetoprolol were obtained from the contralateral arm. RESULTS: Initial pain intensity was 5.9 (arbitrary units) and 5.4 in the groups with and without signs of transmural myocardial damage, respectively. One third of the patients with ST changes reported full pain relief (NRS = 0) within 70 min after starting metoprolol infusion (accumulated dose, 15-180 mg). Among the patients without ST changes upon arrival, full pain relief was obtained in 70% (accumulated dose, 30-120 mg). There was a dose-dependent relation between accumulated metoprolol dose and pain relief. The diagnosis of acute myocardial infarction (AMI) was confirmed in all 15 patients with ECG signs on arrival of transmural myocardial damage. The mean metoprolol dose in this group was 91(12) mg. The mean metoprolol dose in the 12 patients without ST changes was 64(8) mg. In all, seven of these patients developed definite AMI. The terminal half-life of unchanged metoprolol ranged from 2.5 to 8.5 h in group 1 and from 2.2 to 5.2 h in group 2. In group 1, metoprolol half-life was 4.5 h and total plasma clearance (CL) 54.1 1.h-1. In group 2, the metoprolol half-life was 3.7 h and total plasma clearance 75.4 1.h-1. There was a significant difference in clearance between the groups. After the intravenous metoprolol infusion, alpha-hydroxymetoprolol concentrations increased gradually. In groups 1 and 2, maximal concentrations in plasma (Cmax) were 143 and 135 nmol.1(-1) for alpha-hydroxymetoprolol and 2830 and 1653 nmol.1(-1) for metoprolol, respectively. Plasma NA or NPY did not differ between the groups. In contrast, plasma A was significantly higher during the initial 90 min of observation in patients with ECG signs of transmural myocardial damage. CONCLUSION: High-dose intravenous metoprolol was well tolerated in patients with suspected AMI. There was a more rapid and almost complete pain relief in patients without signs of transmural ischaemia compared with the patients with ECG signs of transmural AMI at arrival. In the later group of patients, plasma clearance of metoprolol was significantly reduced.
Aged↗
Effects of calcium antagonist felodipine on renal sympathetic nerve activity in rats with congestive heart failure.
In order to assess the effects of dihydropyridine calcium antagonist on sympathetic nerve activity (SNA) in experimental chronic heart failure (CHF), felodipine was given to rats with CHF induced by coronary artery ligation. Anesthetized CHF (n = 7) and sham-operated (n = 9) rats were injected with a bolus dose of felodipine (20 microg/kg) and then infused with felodipine (30 microg/kg/h) for 3 hours. Control CHF rats (n = 8) were given vehicle in the same way. After felodipine treatment, mean blood pressure (MBP) rapidly decreased to 75-85 mmHg, and there was a reflex tachycardia and reflex activation of renal SNA. The heart rate (HR) had returned to baseline level after 3 hours of continuous felodipine infusion, and the SNA returned to baseline level after 2 hours of infusion. At the end of the experiment, renal SNA was 65.4 +/- 11.5% of the baseline level in CHF rats receiving felodipine (P < 0.05) and 94.1 +/- 22.8% in CHF rats receiving vehicle (P > 0.05), but there was no statistical difference between the two groups. Arterial baroreceptor sensitivity (assessed by phenylephrine infusion), which was impaired in CHF rats (-2.7 +/- 0.2 SNA%/mmHg in all CHF rats together vs. -3.6 +/- 0.4 in sham-operated rats, P < 0.5) did not differ significantly from that in sham-operated rats during felodipine infusion (-3.2 +/- 0.4 in felodipine-treated CHF rats vs. -3.7 +/- 0.6 in sham-operated rats) but deteriorated without felodipine treatment (-2.1 +/- 0.3 in CHF rats receiving vehicle, P < 0.05). The biphasic renal SNA response during felodipine infusion suggests that felodipine does not cause persistent sympathetic activation and relatively improves baroreceptor sensitivity in CHF rats.
Animals↗
Effects of hydralazine on renal sympathetic nerve activity in normal and congestive heart failure rats.
We investigated the effects of hydralazine on renal sympathetic nerve activity in anaesthetized heart failure rats. Sham-operated rats (group 1) received 0.5 mg kg-1 of hydralazine as bolus and were then infused with 0.3-0.5 mg kg-1 h-1 for 3 h intravenously. Heart failure rats received either the same regime (group 2) as group 1, or the same volume of vehicle (group 3). Heart failure rats exhibited lower mean blood pressure (P < 0.05) and elevated renal sympathetic nerve activity (P < 0.01) in the basal state. In group 2, the mean blood pressure decreased 26% after 30 min of hydralazine administration and remained lower for 3 h, with unchanged renal sympathetic nerve activity. In group 1, the mean blood pressure decreased 36%, and the heart rate and renal sympathetic nerve activity were significantly inhibited. Bilateral vagotomy did not alter renal sympathetic nerve response to hydralazine, but resulted in tachycardia. The results indicate that hydralazine, despite its profound hypotensive effect, did not activate renal sympathetic nerve activity in heart failure rats and inhibited renal sympathetic nerve activity in sham-operated rats. This inhibition was not mediated through the vagal nerve.
Animals↗
Effects of 1,1-dimethylguanidine administration on blood pressure, heart rate and renal sympathetic nerve activity in normotensive and spontaneously hypertensive rats.
1,1-dimethylguanidine (DMG) is an endogenous nitric oxide (NO) synthesis inhibitor. This study investigates the effects of exogenous DMG administration, in anaesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Mean blood pressure (MBP), heart rate (HR) and renal sympathetic nerve activity (SNA) were recorded in 12- to 14-week old, anaesthetized SHR and WKY. Each rat received increasing bolus injections of DMG intravenously (1.03, 2.05, 6.39, 20.45 and 51.15 mg kg-1). In separate experiments, SHR received L-arginine or D-arginine in a dose of 300 mg kg-1 followed by DMG at 6.39 mg kg-1. Thirty minutes later they received the same doses of the respective arginines followed by DMG at 20.45 mg kg-1 DMG induced dose-dependant increases in MBP in SHR and WKY. In SHR, HR increased with increasing doses of DMG (except at the near-toxic doses of 51.15 mg kg-1), whereas in WKY HR decreased with increasing doses of DMG. The net change of renal SNA ranged from -5 +/- 3 to -55 +/- 12% in SHR and from -6 +/- 8 to -66 +/- 8% in WKY. Pre-treatment with L-arginine in SHR partly inhibited the pressor effect and attenuated the inhibition of renal SNA induced by DMG, but had little effect on HR. Thus the administration of NO inhibitor DMG could alter cardiovascular function and sympathetic nerve activity, and subsequently resulted in tachycardia in SHR and bradycardia in WKY.
Animals↗
Growth hormone improves cardiac function in rats with experimental myocardial infarction.
Accumulating evidence suggests from experimental and clinical studies beneficial effects of growth hormone (GH) on contractility, although concomitant cardiac hypertrophy, generally considered to be a cardiovascular risk factor, has also been reported. In the present study, we combine a rat model with impaired cardiac performance after myocardial infarction (MI) with echocardiographic evaluation of GH effects on cardiac structure and function. We have used a rat model with ligation of the left coronary artery in normal, growing male rats resulting in subsequent impaired cardiac performance. After 6 weeks' recovery, blind transthoracic echocardiography was performed to determine infarction size, cardiac geometry and performance. Rats with no signs of myocardial infarction were excluded from the study. After randomization, the rats were treated with daily s.c. injections of saline (n = 8) or recombinant human growth hormone (rhGH) (n = 6) at a dose of approximately 1 mg kg-1 body weight for 1 week. A new blind echocardiography examination was performed after treatment demonstrating a 13% increase in ejection fraction (EF) and a 50% increase in cardiac index in GH-treated rats compared with control rats (P < 0.01). Moreover, GH caused a significant decrease in end-systolic volume. There were no significant changes in left ventricular (LV) or interventricular wall thickness, LV dimensions, heart rate or diastolic function. No effects were seen on LV weight, cardiac insulin-like growth factor (IGF) I, IGF-I receptor and GH receptor mRNA content. GH in a physiological dose improves systolic function in an experimental model of heart failure without signs of hypertrophy, suggesting a potential role as a therapeutic agent in the treatment of heart failure and merits further investigation.
Animals↗
Brain natriuretic peptide in an elderly population.
OBJECTIVES: To study the relationship of brain natriuretic peptide concentrations to ageing, and whether brain natriuretic peptide could reflect current disease states in the general elderly population. DESIGN: Brain natriuretic peptide was measured in two population samples from the general population. SUBJECTS: Five hundred forty-five 85-year-old subjects from the longitudinal population study '70-year-old people in Gothenburg, Sweden' were investigated in respect to cardiovascular, renal and metabolic disease, and 191 subjects from the 40-year-old male population were examined. MAIN OUTCOME MEASURES: To study the influence of ageing on circulating brain natriuretic peptide and the association between concentrations of brain natriuretic peptide and common disease states in the elderly. RESULTS: Brain natriuretic peptide concentrations were significantly increased in relation to ageing (P < 0.001). Brain natriuretic peptide concentrations were significantly increased in elderly with congestive heart failure (P < 0.001), ischaemic heart disease (P < 0.001), atrial fibrillation (P < 0.001) and renal dysfunction (P < 0.001) but not in hypertension. In multivariate analysis, brain natriuretic peptide concentrations were predictive for ischaemic heart disease (P < 0.001), atrial fibrillation (P < 0.01), renal dysfunction (P < 0.01), congestive heart failure (P < 0.05) and treatment with beta-adrenergic blockers (P < 0.05). CONCLUSIONS: Plasma concentrations of brain natriuretic peptide are increased in healthy elderly compared to middle-aged individuals. In the elderly, measurements of brain natriuretic peptide may provide prognostic information, due to the augmented secretion in cardiovascular diseases commonly seen in this population. It remains to be determined whether routine measurements of circulating brain natriuretic peptide will be of value in predicting current cardiovascular disease for the individual patient.
Aged↗
Atrial natriuretic peptides predict mortality in the elderly.
OBJECTIVES: To ascertain whether atrial natriuretic peptides could be used as prospective and independent predictors of total mortality in an elderly population. DESIGN: Atrial natriuretic peptides, ANP(1-98) and ANP(99-126), were measured in 541 subjects from the 85-year-old population of Gothenburg, Sweden. Before the study cardiovascular disorders such as congestive heart failure, ischaemic heart disease, hypertension and atrial fibrillation were defined. Total mortality was recorded during the prospective 60-month follow-up period. SETTING: Individuals aged 85 years from the population of Gothenburg, Sweden, were visited once at home and made one visit to Vasa Hospital. MAIN OUTCOME MEASURES: Sixty-month mortality in relation to circulating concentrations of atrial natriuretic peptides. RESULTS: Circulating concentrations of ANP(1-98) and ANP(99-126) were significantly correlated with 60-month mortality in the total study population (ANP(1-98), P < 0.001: ANP(99-126), P < 0.01). In subjects with cardiovascular disorders, 60-month mortality was significantly correlated with increased concentrations of ANP(1-98) (P < 0.01) and ANP(99-126) (P < 0.05). In subjects with no defined cardiovascular disorder, 60-month mortality was significantly correlated with increased ANP(1-98) concentrations (P < 0.01). CONCLUSIONS: In the elderly population, atrial peptides predict mortality in subjects with defined cardiovascular disorders as well as in the total population and may predict future cardiovascular disorder.
Aged↗
Does the neuropeptide Y Y1 receptor contribute to blood pressure control in the spontaneously hypertensive rat?
OBJECTIVE: To study the effects of the selective neuropeptide Y (NPY) Y1 receptor antagonist BIBP 3226 in spontaneously hypertensive rats (SHR) in order to elucidate whether NPY function may be altered in the SHR and whether the NPY Y1 receptor plays a specific role in the maintenance of high blood pressure in this genetic form of hypertension. METHODS: Pithed and conscious SHR were studied after intravenous administration of 0.125-1 mg/kg BIBP 3226. The cardiovascular effects were evaluated under baseline conditions, under acute stress and after exogenous administration of 20 microg/kg NPY. The potentiating effects of NPY on pressor responses to phenylephrine and tyramine were studied in the SHR. RESULTS: Intravenous administration of 0.125-1 mg/kg BIBP 3226 dose-dependently inhibited the pressor response to exogenous NPY in pithed SHR. At higher doses BIBP 3226 had an effect duration of 20-40 min. In the pithed SHR, a 0.5 mg/kg bolus injection of BIBP 3226 shifted the pressor response curve for exogenous NPY significantly to the right It also inhibited significantly the potentiating effects of NPY on pressor responses to phenylephrine and tyramine. In conscious SHR, 0.125-1 mg/kg BIBP 3226 did not reduce the basal blood pressure. In combination with a hypotensive dose of prazosin, administration of 0.5 mg/kg BIBP 3226 had no added effects lowering the basal blood pressure. A stressful stimulus, namely an air jet, caused a brief increase in blood pressure and heart rate in the conscious SHR. In this model, 0.5 mg/kg BIBP inhibited the heart rate response slightly but had no effect on the blood pressure response. CONCLUSIONS: Our results demonstrate that, although the selective NPY Y1 receptor antagonist BIBP 3226 may shift the pressor response to exogenous NPY potently, it does not influence basal blood pressure significantly in the SHR.
Animals↗
Brain natriuretic peptide predicts mortality in the elderly.
OBJECTIVE: To study whether prospective measurements of circulating concentrations of brain natriuretic peptide (BNP) could predict mortality in the general elderly population. DESIGN AND SETTING: Circulating BNP was measured in a cohort of 85 year olds from the general population who were followed up prospectively for five years as part of a longitudinal population study, "70 year old people in Gothenburg, Sweden". PATIENTS: 541 subjects from the 85 year old population in Gothenburg. All subjects were investigated for the presence or absence of cardiovascular disorder such as congestive heart failure, ischaemic heart disease, hypertension, and atrial fibrillation. Venous plasma samples were obtained for BNP analysis. MAIN OUTCOME MEASURE: Overall mortality during the prospective follow up period. RESULTS: Circulating concentrations of BNP predicted five-year mortality in the total population (P < 0.001). In subjects with a known cardiovascular disorder, five-year mortality was correlated with increased BNP concentrations (P < 0.01). Increased BNP concentrations predicted five-year mortality in subjects without a defined cardiovascular disorder (P < 0.05). CONCLUSIONS: In an elderly population, measurements of BNP may add valuable prognostic information and may be used to predict mortality in the total population as well as in patients with known cardiovascular disorders. In subjects without any known cardiovascular disorder, BNP was a strong and independent predictor of total mortality.
Aged↗
Psychosocial factors and blood pressure. Why are nuns better off?
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Blood Pressure↗
Is hypertension a risk factor for cancer?
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Humans↗
The enigmatic association of birth weight with blood pressure.
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Adolescent↗
Calcium antagonists--looking stronger by the day.
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Aged↗
Unsatisfactory blood pressure control--patient's neglect or doctor's hesitation?
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Antihypertensive Agents↗