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Biomedical subjects

T Thien

Publications and source records attributed to T Thien.

At least 145 records · Page 8Linked to original sources

Effect of NG-monomethyl-L-arginine on the beta-adrenoceptor-mediated relaxation of rat mesenteric resistance arteries.

beta-Adrenoceptors are present on vascular smooth muscle and on endothelium. We investigated whether the endothelial beta-adrenoceptors induce relaxation of rat mesenteric resistance arteries by stimulation of endothelium-derived relaxing factor (EDRF) release. To this end, the relaxation was studied in the presence and absence of 100 microM NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of the production of EDRF. The maximal relaxation with isoprenaline, expressed as a percentage of the precontraction, was 44.0 +/- 4.0% (n = 12) in the L-NMMA treated group and 58.0 +/- 2.6% (n = 13) in the untreated group, a statistically significant difference (P = 0.008). However, the precontraction with 40 mM K+ tended to be higher in the presence of L-NMMA. The pD2-value for isoprenaline was not significantly changed by the L-NMMA treatment. We conclude that the isoprenaline-mediated relaxation of mesenteric resistance arteries is inhibited by L-NMMA, but that this effect can at least in part be ascribed to an inhibition of baseline EDRF-release.

Animals↗

The cardiovascular interaction between caffeine and nicotine in humans.

In a placebo-controlled, double-blind randomized design, we investigated the cardiovascular interaction between caffeine (250 mg intravenously) and nicotine (4 mg chewing gum) in 10 healthy volunteers, both under baseline conditions and during physical and mental stress (standing up and mental arithmetic). Caffeine alone induced a significant increase in blood pressure associated with a decrease in heart rate, whereas nicotine alone increased both blood pressure and heart rate. The combination of caffeine and nicotine increased systolic and diastolic blood pressure by 10.8 +/- 2.0 and 12.4 +/- 1.9 mm Hg, respectively. This pressor response did not differ significantly from the calculated additive effects of caffeine and nicotine on blood pressure, measuring 12.9 +/- 2.0 and 14.2 +/- 2.1 mm Hg, respectively. Heart rate and forearm blood flow also showed a similar response when the combination of caffeine and nicotine was compared with the calculated sum. During physical stress (standing up), blood pressure, heart rate, and plasma catecholamines increased in the placebo test. The pressor response to standing up was less pronounced after the combination of caffeine and nicotine compared with the sum of the separate effects (combination versus sum: delta diastolic blood pressure, 24.7 +/- 1.9 versus 35.2 +/- 2.6 mm Hg [p < 0.01]; delta mean arterial pressure, 22.1 +/- 2.0 mm Hg versus 28.6 +/- 1.6 mm Hg [p < 0.05]). The plasma catecholamine response did not differ between the combination and the sum of both drugs. During mental arithmetic, blood pressure, heart rate, and forearm blood flow increased in the placebo test. The forearm vasodilator response to mental stress was attenuated by the combination of caffeine and nicotine compared with the sum of both drugs (combination versus sum: delta forearm blood flow, -0.1 +/- 0.3 versus 1.4 +/- 0.5 ml/100 ml/min [p < 0.05]). We conclude that the combined administration of caffeine and nicotine shows additive effects on cardiovascular parameters during baseline conditions but less than additive effects during sympathoadrenal stimulation.

Adult↗

Effect of chronic smoking on endothelium-dependent vascular relaxation in humans.

1. Cigarette smoking is one of the major risk factors for the development of atherosclerosis. It is not clear, however, whether chronic cigarette smoking impairs the normal physiological function of the endothelium before the development of morphological vascular lesions. To test this, we investigated endothelium-dependent vascular relaxation in young habitual smoking subjects. 2. In 11 non-smokers and 10 habitual smokers we measured the changes in bilateral forearm blood flow, arterial blood pressure and forearm vascular resistance (ratio between mean arterial blood pressure and forearm blood flow) during three interventions: post-occlusive forearm hyperaemia, intrabrachial infusion of methacholine which causes vasodilatation by stimulating the release of endothelium-dependent relaxing factor, and intrabrachial infusion of sodium nitroprusside which causes vasodilatation independently from the endothelium by a direct effect on the vascular smooth muscle wall. 3. During infusion of the highest dose of methacholine, forearm vascular resistance decreased by 91.7 +/- 1.4% in the smokers and by 89.9 +/- 1.8% in the non-smokers. During infusion of sodium nitroprusside, forearm vascular resistance decreased by 80.0 +/- 3.8% in the smokers as compared with 80.7 +/- 6.1% in the non-smokers. There was no difference in basal forearm vascular resistance or in post-ischaemic reactive hyperaemia between smokers and non-smokers. Thus, vasodilatation induced by both methacholine and sodium nitroprusside was not significantly different between smokers and non-smokers. 4. We conclude that in young habitual cigarette smokers the endothelium-dependent vasodilation in the forearm seems to be preserved, suggesting that habitual smoking does not result in permanent endothelial dysfunction in the human forearm.

Adult↗

Accuracy and reproducibility of 30 devices for self-measurement of arterial blood pressure.

Thirty commercially available noninvasive devices for self-measurement of blood pressure were tested for accuracy and reproducibility against intraarterial measurement in 15 normotensive and 15 hypertensive subjects. For reference to outpatient measurements, a standard sphygmomanometer was included. Analysis of the data for any device was performed according to a statistical model in which two types of errors, representing accuracy and reproducibility, were distinguished: offset (mean difference between intraarterial measurement and device) and standard deviation (comprising intraindividual and interindividual variability). Linearity of the devices was analyzed by linear regression with intraarterial measurement as independent variable. The average offset of all tested devices amounted to 11.7 mm Hg (ranging from -0.2 to 21.4 between instruments) for systolic blood pressure and -1.6 mm Hg (range -11.4 to 8.1) for diastolic blood pressure. The standard deviation between instruments ranged from 7.0 to 15.4 mm Hg for systolic and from 3.3 to 16.0 mm Hg for diastolic blood pressure. Except for the devices based on the oscillometric principle, most (semi-) automated devices demonstrated a variability similar to the mercury sphygmomanometer (offset = 14.3 for systolic and 0.1 mm Hg for diastolic pressure; standard deviation = 7.5 for systolic and 5.6 mm Hg for diastolic blood pressure). Devices based on the oscillometric principle had a significantly larger variability. It is concluded that new devices should be tested for accuracy and reproducibility before application for clinical use. Blood pressure measurements from instruments with larger offset are only comparable to values from other instruments after rescaling in accordance with their offset.

Adult↗

A standardized finger cooling test for Raynaud's phenomenon: diagnostic value and sex differences.

In 99 patients with primary Raynaud's phenomenon (RP), in 97 with secondary RP and in 101 healthy subjects, finger skin temperature and laser Doppler flux were measured before, during and after immersion of the hand in a 16 degrees C water bath. We determined the baseline value, the values at the end of the cooling period and after 12 and 20 min of recovery, the percentual decrease during cooling and the mean values during cooling, during recovery and during the whole test. Most of the finger skin temperature and laser Doppler flux parameters were significantly lower in females than in males in all three groups. There were no significant differences between patients with either primary or secondary RP. In both sexes, all test parameters (with the exception of the percentual decrease during cooling) were significantly lower in the patients with RP than in healthy subjects. With a diagnostic specificity of 70%, the sensitivity varied between 55% and 81% for the different test parameters. Although, in both sexes, finger skin temperature and laser Doppler flux values before, during and after cooling were significantly lower in patients with RP than in healthy subjects, the considerable overlap between both groups limits the diagnostic value in individual cases.

Adult↗

Adrenoceptors on blood cells in patients with primary hypertension: correlation with blood pressure and related variables.

OBJECTIVE: Alterations in platelet alpha 2-adrenoceptor and mononuclear leucocyte beta 2-adrenoceptor characteristics in primary hypertension have been extensively studied. The results of the reports have not been consistent, possibly because of the small number of subjects in most of the studies. We therefore studied the blood-cell adrenoceptor characteristics in a relatively large group of primary hypertensive and normotensive subjects. DESIGN: Platelet alpha 2-adrenoceptor characteristics were compared in 65 hypertensive and 51 normotensive subjects. Mononuclear leucocyte beta 2-adrenoceptor characteristics were compared in 72 hypertensives and 67 normotensives. Untreated hypertensive subjects were selected from the outpatient clinic and the normotensive controls were recruited by a newspaper announcement. METHODS: Platelets and mononuclear leucocytes were isolated from blood samples obtained after at least 10 min supine rest. The alpha 2- and beta 2-adrenoceptor characteristics were determined with [3H]-rauwolscine and [125I]-(-1)cyanopindolol, respectively. Correlations between the adrenoceptor characteristics and clinical parameters of the subjects were studied. RESULTS: No differences in alpha 2- or beta 2-adrenoceptor densities were observed between the two groups. However, a significantly lower equilibrium dissociation constant for [3H]-rauwolscine was observed in the hypertensive group. The correlations between the adrenoceptor characteristics and clinical parameters were weak and mostly not statistically significant. The results were compared with the most relevant studies in the literature. CONCLUSIONS: From our study and the literature, we conclude that blood-cell adrenoceptor characteristics are unchanged in primary hypertension.

Adult↗

Forskolin-stimulated adenylyl cyclase activity is decreased but beta 2-adrenoceptor function is unchanged in primary hypertension.

beta 2-Adrenoceptor function may be decreased in primary hypertension, resulting in increased peripheral resistance. To study the beta 2-adrenoceptor function, we used circulating mononuclear leukocytes (MNL) as a model system. Twenty untreated hypertensive subjects [(HT) 10 men and 10 women] and 20 age- and sex-matched healthy normotensive (NT) volunteers were studied. The beta 2-adrenoceptor density was not significantly different between HT and NT, but the dissociation constants for the high- and low-affinity agonist binding states, studied by isoprenaline competition assays, were significantly higher in HT. Stimulation of adenylyl cyclase with isoprenaline (10 microM, beta 2-adrenoceptor-mediated stimulation) was not significantly different between the two groups. Forskolin-mediated direct stimulation of adenylyl cyclase was significantly higher in women than in men. For both sexes, the forskolin-induced cyclic AMP production was lower in the HT group, reaching statistical significance in the men. No major abnormalities were observed in beta 2-adrenoceptor function in mononuclear leukocytes. The putative relation between the decreased forskolin-mediated adenylyl cyclase activity and primary hypertension requires further study.

Adenylyl Cyclases↗

NG-monomethyl-L-ARG reduces the forearm vasodilator response to acetylcholine but not to methacholine in humans.

We compared the contribution of nitric oxide (NO) in methacholine (MCh)- and acetylcholine (ACh)-induced vasodilation using the NO-synthase inhibitor NG-monomethyl-L-arginine acetate (L-NMMA-acetate) in two groups (A and B) of 6 healthy male volunteers. The left brachial artery was cannulated for drug infusion and recording of mean arterial pressure (MAP). Forearm blood flow (FBF) was measured on both sides by venous occlusion mercury-in-silastic strain-gauge plethysmography. All measurements were performed with occluded hand circulation. Forearm vasodilator response to three increasing dosages of MCh (0.03, 0.3, and 1 micrograms/100 ml forearm/min; group A) or ACh (0.5, 2, and 8 micrograms/100 ml forearm/min; group B) was studied first. Forty-five minutes later, these infusions were repeated (after and during local administration of L-NMMA). L-NMMA-acetate infusion alone increased basal forearm vascular resistance (FVR, mean +/- SE) by 86.2 +/- 14.5 and 99.5 +/- 27.4% in groups A and B, respectively (p < 0.05) without significant FVR changes in the control arm. MCh-induced vasodilation was not attenuated by concomitant L-NMMA-acetate infusion. In contrast, L-NMMA-acetate significantly reduced the averaged percentage decrease in FVR during infusion of ACh from 55.7 +/- 9.1 to 35.4 +/- 11.8% (p < 0.05). L-NMMA-acetate increased basal vascular tone and reduced the vasodilator response to ACh. MCh induced vasodilation to a degree similar to that obtained with ACh. Nevertheless, MCh-induced vasodilation could not be attenuated by L-NMMA, suggesting that NO contributes differentially to methacholine- and ACh-induced vasodilation in humans.

Acetylcholine↗

Comparison of cyclic guanosine monophosphate response to infusion of atrial natriuretic peptide in young and elderly subjects.

OBJECTIVE: To compare the sensitivity to atrial natriuretic peptide (ANP) in young and elderly subjects. DESIGN: Double-blind, random-order, placebo-controlled study using two different rates of ANP infusion. SUBJECTS: Eight healthy young (23 +/- 3 years, mean +/- SD) and eight healthy elderly (76 +/- 4 years) subjects recruited from the general population. MEASUREMENT: Plasma cyclic guanosine monophosphate (cGMP, the second messenger of ANP) levels reflecting the sensitivity of biologically active ANP receptors. RESULTS: Baseline ANP levels were higher and rose to a greater extent in the elderly both during low- (0.25 microgram/min) and high-dose (2.0 micrograms/min) infusion of ANP. Plasma levels of cGMP rose in proportion to the increase in ANP. When the rise in cGMP levels was related to the increase in ANP levels (expressed as nmol/L per 100 pg/mL ANP increase), no difference was found between young and elderly subjects. CONCLUSION: The ability of elderly subjects to increase cGMP in response to exogenous ANP is similar to that of young subjects. This may reflect a similar sensitivity of the target organs towards ANP. However, because of lower clearance in the elderly, a similar dose of ANP results in a greater elevation of ANP and cGMP levels and hence induces a greater effect.

Adult↗

Skin vascular reactivity in healthy subjects: influence of hormonal status.

To investigate the influence of the hormonal status on skin vascular reactivity, 18 males, 18 women using oral contraceptives (oc), 17 premenopausal, and 18 postmenopausal women were studied. Finger skin temperature (FST, in degrees C) and laser Doppler flux (LDF, in perfusion units) were measured during heating (45 degrees C water bath) and cooling (15 degrees C) followed by a subsequent recovery period. Maximal heat-induced vasodilation was significantly higher in women using oc and in premenopausal women when compared with males. During cooling, FST and LDF were significantly higher in males compared with women using oc and premenopausal women, respectively. FST was also higher in postmenopausal women than in women using oc. During recovery, FST and LDF were significantly higher in males than in women using oc, and LDF was also higher in males than in premenopausal women. These findings are consistent with a less pronounced and less prolonged cold-induced vasoconstriction in males. Other hemodynamic (blood pressure or heart rate) or biological factors (age, amount of subcutaneous fat, hand volume, or body mass index) that possibly influence peripheral blood flow were found not to influence the results. The observed differences in vascular reactivity toward temperature changes between subjects with a different hormonal status suggest that sex hormones influence finger skin perfusion.

Adolescent↗

Atrial natriuretic peptide. An overview of clinical pharmacology and pharmacokinetics.

The atrial natriuretic peptide (ANP) is part of a new family of cardiac hormones regulating water and salt homeostasis. Besides acting as a blood pressure-lowering agent, it also exerts potent natriuretic and diuretic effects. ANP can be considered an endogenous antagonist of the reninangiotensin-aldosterone system and the antidiuretic hormone. One of the roles of ANP is to protect the body against fluid overload: it decreases intravascular fluid volume, which in turn diminishes cardiac secretion of ANP. The pharmacokinetic parameters of ANP reported in the literature vary widely. In general, ANP rapidly disappears from plasma with a high total body clearance. This is in agreement with the short-lived effects of the hormone. The actions of ANP have led to efforts to use this peptide hormone in the treatment of various cardiovascular disorders such as hypertension and congestive heart failure. Intravenous ANP administration indeed resulted in beneficial effects in these disorders. However, the peptide nature of ANP and its rapid elimination from the circulation limit its suitability as a drug. More promising is the development of long-acting ANP analogues and inhibitors of ANP degradation. Proper understanding of ANP pharmacokinetics is essential for the clinical use of these pharmacological agents.

Animals↗

Endothelium-dependent vascular relaxation in patients with type I diabetes.

The endothelium plays an important role in the regulation of vascular tone. Although animal data show evidence for an impaired endothelium-dependent vasodilation in diabetes, human in vivo data are scarce. We investigated 11 type I diabetic patients and 11 matched healthy control subjects. The diabetic patients were selected on their relatively poor metabolic regulation (HbA1c > 8.5%), but none showed signs of microvascular complications. In all subjects, we recorded the forearm vasodilator responses to three different stimuli: 1) 5 min of forearm ischemia to obtain a maximal vasodilator response; 2) infusion of MCh into the brachial artery (dosages: 0.03-0.3-1.0 micrograms.min-1.100 ml-1 forearm volume) to evaluate endothelium-dependent vasodilation; and 3) intra-arterial infusion of SNP (dosages: 0.06-0.2-0.6 micrograms.min-1.100 ml-1) to evaluate endothelium-independent vasodilation. The diabetic patients had their usual subcutaneous insulin dose and breakfast 90 min before the start of the test. Baseline levels of BP and FBF were similar in both groups. The PORH response was similar in both groups, with a percentage fall in FVR of 92 +/- 1% in diabetic patients and 94 +/- 1% in control subjects. In the control subjects, MCh infusions exerted a dose-dependent vasodilator response with a maximal fall in the FVR of 90 +/- 2%. The highest dose of SNP induced a fall in FVR of 81 +/- 6% in this group. In diabetic patients, the percentage decrements in FVR during the several dosages of MCh and SNP were similar when compared with the control group. We conclude that chronic hyperglycemia, as occurred in our patients with uncomplicated diabetes mellitus, does not impair endothelium-dependent vasodilation in vivo.

Adult↗

Impaired vasodilator response to atrial natriuretic factor in IDDM.

Diabetes mellitus has been associated with both elevated plasma concentrations of the natriuretic and vasorelaxant hormone atrial natriuretic factor and with a reduced natriuretic response to this hormone. We now hypothesize that the vasodilator response to atrial natriuretic factor is attenuated in IDDM. Forearm vasodilator responses to the infusion of six increasing dosages of atrial natriuretic factor into the brachial artery were registered by venous occlusion strain gauge plethysmography in 10 patients with uncomplicated IDDM and in 10 age-, sex-, and weight-matched control subjects. Baseline levels of blood pressure, forearm blood flow, and plasma concentrations of atrial natriuretic factor were not different between control subjects and patients with diabetes. In control subjects, atrial natriuretic factor induced a percentage fall in the forearm vascular resistance of -29 +/- 5% at the lowest to -72 +/- 4% at the highest infusion rate. In patients with diabetes this fall was significantly attenuated, measuring -2 +/- 7 and -45 +/- 4%, respectively, (P < 0.001 vs. control subjects). During infusion of atrial natriuretic factor into the brachial artery, the calculated regional production of cGMP (second messenger of atrial natriuretic factor) increased from 1.2 +/- 1.1 to 22.8 +/- 4.8 pmol.min-1 x 100 ml-1 in the control subjects, whereas hardly any change occurred in the patients with diabetes (from -2.1 +/- 1.2 to 2.9 +/- 4.7 pmol.min-1 x 100 ml-1). Furthermore, both control and diabetic subjects demonstrated an equal forearm vasodilator response to increasing infusion rates of the control vasodilator sodium nitroprusside. We conclude that uncomplicated IDDM is associated with a specific reduction in the vascular responsiveness to atrial natriuretic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The relationship between subjective vasospastic complaints and finger blood flow measurements in Raynaud's phenomenon.

BACKGROUND: Objective circulatory tests in patients with Raynaud's phenomenon have only rarely been related to subjective complaints. METHODS: In 55 Raynaud patients the correlation between daily self-recorded frequency, duration and severity of vasospastic attacks and the measurement of finger skin blood flow during local cooling was investigated. RESULTS: No significant correlations were found between complaints as registered in the diaries and finger skin temperature and laser Doppler flux before, during and after a standardized local cooling procedure. CONCLUSION: Finger skin blood flow measurements do not necessarily reflect digital vasospasm in daily life. Besides studies on the diagnostic value and reproducibility of skin blood flow measurements in Raynaud's phenomenon, the relationship of test results to subjective complaints should be established.

Activities of Daily Living↗

Prevalence of left ventricular hypertrophy as assessed by electrocardiogram in treated hypertensive persons in general practice.

Many studies have paid attention to the prevalence of left ventricular hypertrophy (LVH) as assessed by electrocardiogram (ECG) in hypertensive patients. Patients with ECG-LVH show a considerably higher risk of cardiovascular morbidity and mortality than patients without ECG-LVH. This paper describes the prevalence of LVH and the relation between LVH, age, sex and BP. ECG, BP, treatment, duration of hypertension, body mass index and total serum cholesterol were recorded. The dimension of LVH was computed in accordance with the Minnesota Code. One of five hypertensive patients (21%) had LVH with or without repolarisation abnormalities. LVH based on high QRS voltages only was found more often in men. LVH with repolarisation abnormalities was more frequent in elderly patients. LVH was found more often in the highest SBP categories (SBP > 160 mmHg) and in the highest DBP categories (DBP > 105 mmHg). A logistic regression analysis showed the influence on the occurrence of LVH of the following parameters: being male, age > 65 years, SBP > 160 mmHg and DBP > 105 mmHg.

Aged↗