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Biomedical subjects

T Thien

Publications and source records attributed to T Thien.

At least 127 records · Page 7Linked to original sources
PubMed1995

Hydrochlorothiazide exerts no direct vasoactivity in the human forearm.

BACKGROUND: Recently, hydrochlorothiazide has been shown to relax vascular smooth muscle in vitro in clinically relevant concentrations by the opening of calcium-activated potassium channels, leading to hyperpolarization and consequent closing of voltage-operated calcium channels. Long-term administration of hydrochlorothiazide reduces peripheral vascular resistance in vivo in man. These results indicate that hydrochlorothiazide has hemodynamic activity, and we therefore examined the direct vascular action of this drug in vivo. SUBJECTS AND METHODS: Forearm vasodilator responses to the infusion of a placebo and five increasing doses of hydrochlorothiazide into the brachial artery were recorded by venous occlusion strain-gauge plethysmography (perfused forearm technique) in eight normotensive male volunteers. Venous samples were taken from an ipsilateral antecubital vein at the end of each infusion period to measure the hydrochlorothiazide concentration. RESULTS AND DISCUSSION: Plasma concentrations of hydrochlorothiazide averaged 3.5 +/- 0.3 mu g/ml at the highest infusion rate. This concentration leads to a 60 +/- 10% relaxation in vitro and is more than 10 times the therapeutic plasma concentration. Despite these supratherapeutic levels, we were unable to demonstrate a change in forearm blood flow and vascular resistance. Also, no significant changes were observed in blood pressure and heart rate. CONCLUSION: In contrast to in vitro results, hydrochlorothiazide does not exert any direct vasoactivity in the forearm vascular bed of healthy normotensive male volunteers at (supra)therapeutic plasma concentrations.

Antihypertensive Agents↗
PubMed1995

Chronic alpha-1-adrenergic blockade increases sympathoneural but not adrenomedullary activity in patients with essential hypertension.

OBJECTIVE: Doxazosin, a selective alpha1-adrenoceptor antagonist, lowers blood pressure by reducing peripheral vascular resistance without causing reflex tachycardia. To discover whether antihypertensive treatment with an alpha1-adrenoceptor blocker is accompanied by an increase in sympathoadrenomedullary activity, we studied plasma catecholamine kinetics before and during treatment with doxazosin. PATIENTS AND METHODS: Eleven patients with essential hypertension were studied before and after 3 months' treatment with doxazosin (4-8 mg a day). 3H-noradrenaline and 3H-adrenaline were infused simultaneously and blood samples were collected to calculate plasma catecholamine kinetics before and during sympatho-adrenomedullary stimulation (lower-body negative pressure). RESULTS: Doxazosin decreased systolic and diastolic blood pressure and forearm vascular resistance, whereas the heart rate did not change significantly. During doxazosin, baseline arterial plasma noradrenaline increased from 0.97 +/- 0.07 to 1.21 +/- 0.07 nmol/l, and this appeared to be due to an increase in total body noradrenaline spillover from 1.54 +/- 0.15 to 1.84 +/- 0.16 nmol/min; noradrenaline clearance did not change significantly. Forearm noradrenaline spillover also increased, from 0.89 +/- 0.18 to 1.48 +/- 0.23 pmol/100 ml per min. In contrast, arterial plasma adrenaline, total body adrenaline spillover and adrenaline clearance were not significantly affected by doxazosin treatment. The response of plasma noradrenaline and total body and forearm spillover of noradrenaline to lower-body negative pressure (-40 mmHg) was significantly increased during doxazosin administration, whereas the response of the adrenaline kinetic parameters were not altered. CONCLUSIONS: The blood pressure reduction induced by a chronic administration of the alpha1-adrenoceptor blocker doxazosin elicits a baroreceptor-mediated reflexive increase in sympathoneural but not in adrenomedullary activity. The latter finding might partly explain why the heart rate is not increased during chronic treatment with this alpha1-adrenoceptor blocking drug.

Adrenergic alpha-Antagonists↗
PubMed1994

[A single blood pressure reading during check-up for hypertension leads to a change in management more often than multiple readings].

OBJECTIVE: To define the number of blood pressure readings necessary during a patient's visit to serve as a correct reference for patient management. DESIGN: Observational study. SETTING: Outpatient clinic in the Netherlands. METHOD: In a period of 30 months blood pressure was measured in 250-300 patients with hypertension during 1008 patients' visits. All readings were done by the same physician in the same room with the same system, after the patients had been submitted to at least 10 minutes of supine rest. Three readings were taken simultaneously with a mercury sphygmomanometer and (via a Y-connector) with a semiautomatic oscillometric method. RESULTS: Blood pressure readings of 932 visits were available for further analysis. Both methods gave similar results for the mean of each reading and for the combination of 2 or 3 readings. Based on the first diastolic reading alone instead of the mean of 3 readings, 25% of the patients would have been subjected to different patient management. On the basis of the first two readings II% would have been treated differently. CONCLUSION: No definite recommendation can be made for the ideal number of blood pressure readings per visit, but with only 1 or 2 readings, 11-25% of the subjects would have been submitted to different management.

Blood Pressure Determination↗
PubMed1994

The effects of single oral doses of 17 beta-oestradiol and progesterone on finger skin circulation in healthy women and in women with primary Raynaud's phenomenon.

The effects of sex, the menstrual cycle, oral contraceptives, pregnancy, and the menopause on skin perfusion in healthy women and in patients with Raynaud's phenomenon suggest a role of female sex hormones. However, no clear relation between skin blood flow and circulating concentrations of oestrogens or progestogens has yet been found. The aim of this study was to investigate the effect of orally administered 17 beta-oestradiol and progesterone on finger skin blood flow before and during heat and cold challenge in 17 healthy normotensive women and in 12 women with Raynaud's phenomenon. In each subject standardized finger heating (45 degrees C water bath, 10 min) and cooling tests (15 degrees C water bath, 5 min and 20 min recovery) were performed twice on the second (or third) day of two consecutive menstrual cycles. 17 beta-Oestradiol (9 mg) or progesterone (300 mg) were given before the second test, after a first test with placebo. Both hormonal doses resulted in (high) physiological concentrations. Fingertip skin temperature and laser Doppler flux were measured. There were no significant differences in the test results after placebo and after progesterone. Although values of fingertip skin temperature and laser Doppler flux after 17 beta-oestradiol tended to be higher only the precooling values in the healthy subjects reached significance: fingertip skin temperature respectively with placebo and with oestradiol (mean (SD)): 32.7 (1.0) and 33.1 (0.8) degrees C; laser Doppler flux with placebo and with oestradiol: 33.6 (11.7) and 42.2 (9.5) perfusion units; both P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Atrial natriuretic factor potentiates the human forearm vasoconstrictor response to sympathetic stimulation.

1. Atrial natriuretic factor has been suggested to affect human sympathetic nervous system activity. The interaction between atrial natriuretic factor and the sympathetic nervous system has not been fully elucidated yet, but may occur at different sites. We studied this modulator effect at the level of the forearm vascular bed: the forearm vasoconstrictor response was examined after alpha-adrenergic sympathetic stimulation in healthy subjects during the locoregional administration of atrial natriuretic factor, sodium nitroprusside and placebo. As a sympathetic stimulation test, the technique of the lower body negative pressure (-20 mmHg) was used. 2. Lower body negative pressure increased the forearm vascular resistance by +37 +/- 8% during concomitant intra-arterial infusion of placebo (n = 10). During a predilator state achieved by infusion of atrial natriuretic factor (10 ng min-1 100 ml-1 forearm volume) into the brachial artery, lower body negative pressure subsequently induced a forearm vasoconstrictor response of +153 +/- 22% (P < 0.05 versus placebo), whereas this was +64 +/- 14% when predilatation was achieved by infusion of an equipotent vasodilator dose of sodium nitroprusside (P > 0.1 versus placebo; P < 0.05 versus atrial natriuretic factor). The potentiation of the forearm vasoconstrictor response to lower body negative pressure by atrial natriuretic factor only occurred in the experimental and not in the contralateral arm. According to calculations on simultaneously sampled arterial and venous plasma catecholamine concentrations, the augmented forearm vasoconstrictor response seemed not to be caused by an increased release of noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Quantification of Ca(2+)-ATPase in erythrocytes from subjects with essential hypertension or Raynaud's phenomenon.

The increased peripheral vascular resistance in subjects with essential hypertension and in subjects with primary Raynaud's phenomenon is thought to be the consequence of an impaired control of intracellular Ca2+ in vascular smooth muscle cells. Abnormal membrane handling of Ca2+ in human essential hypertension is not limited to vascular smooth muscle cells but has been demonstrated in a number of blood cells, for example, erythrocytes. Ca(2+)-ATPase activity and Ca(2+)-ATPase densities were measured in erythrocyte membranes from healthy volunteers and subjects with essential hypertension or with Raynaud's phenomenon. We found no significant differences between the three groups in the Ca(2+)-ATPase activity and in the number of Ca(2+)-ATPase immunoreactive sites per erythrocyte. Furthermore, we could not demonstrate any influence of sex or age on these two parameters. We conclude that, in essential hypertension and in Raynaud's phenomenon, the Ca2+ extrusion capacity of the erythrocytes is not altered.

Adult↗
PubMed1994

Vascular effects of pentoxifylline in humans.

In this study, we investigated the vasoactive effects of the alkylxanthine pentoxifylline and its interaction with the nucleoside adenosine in the forearm skeletal muscle vascular bed of 18 normotensive healthy volunteers. Pentoxifylline infusion into the brachial artery in dosages of 100, 300, and 1,000 micrograms/100 ml forearm volume (FAV)/min, induced increments of forearm blood flow (FBF) of 41 +/- 6, 125 +/- 22, and 295 +/- 57%, respectively (n = 12). Calculated forearm vascular resistance (FVR) showed a dose-dependent decrease during pentoxifylline infusion. Concomitant administration of caffeine (100 micrograms/100 ml/min), an adenosine antagonist, did not attenuate the vasodilator response to pentoxifylline (n = 6). Intraarterial (i.a.) infusion of adenosine alone (0.75, 1.5, 3.0, and 4.5 micrograms/100 ml/min) induced a dose-dependent forearm vasodilator response. Concomitant infusion of pentoxifylline (100 micrograms/100 ml/min) did not cause a convincing potentiation of the forearm vasodilator effect of adenosine. This study demonstrates that pentoxifylline induces vasodilation in human forearm skeletal muscle vascular bed of healthy young volunteers. This vasodilator response occurred at concentrations that are probably much higher than those achieved with oral treatment with pentoxifylline. Our data further suggest that pentoxifylline-induced vasodilation is not mediated by adenosine receptor stimulation, but may result from inhibition of the enzyme phosphodiesterase (PDE).

Adenosine↗
PubMed1994

Characterization of ATP-induced vasodilation in the human forearm vascular bed.

BACKGROUND: Animal data indicate that ATP derived from aggregating thrombocytes or endothelium induces an endothelium-dependent vasodilator response that is mediated by P2y-purinergic receptors and is reduced when high dosages are administered. This reduced vasodilator response to high ATP doses has been associated with the concomitant release of endothelium-derived contracting factors. In contrast to the endothelium-dependent vasodilator response, ATP as released from sympathetic nerve endings induces a P2x-purinergic receptor-mediated vasoconstrictor response that may contribute to the attenuated vasodilator response to high dosages of luminally applied ATP. The dual action of ATP might be important in the pathophysiology of disease states characterized by an impaired endothelial function and increased thrombocyte aggregation. This study was performed to characterize the vascular response to ATP in humans. METHODS AND RESULTS: The brachial artery was cannulated in 50 healthy male volunteers (age, 18 to 44 years) for drug infusion and measurement of mean arterial pressure. Forearm blood flow was recorded by venous occlusion strain-gauge plethysmography. ATP induced a dose-dependent vasodilator response that was significantly higher than the effect of equimolar adenosine infusion and that was not reduced by concomitant infusion of the P1-purinergic receptor antagonist theophylline. The infusion of the NO synthase antagonist NG-monomethyl-L-arginine (L-NMMA) reduced the average fall in forearm vascular resistance (FVR) to acetylcholine (-59 +/- 6% [mean +/- SEM] versus -42 +/- 8%; P < .05; N = 10) but did not affect the vasodilator response to ATP (-68 +/- 3% versus -64 +/- 6%; P > .1; N = 10) or sodium nitroprusside (SNP; -53 +/- 3% versus -49 +/- 4%; P > .01; N = 6). The L-NMMA-induced increase in FVR appeared to be related to the type of vasodilator pretreatment, being 94.7 +/- 16.7%, 44.9 +/- 8.7%, and 40.8 +/- 7.3% for acetylcholine, ATP, and SNP pretreatment, respectively (P < .01 for acetylcholine versus ATP and SNP; P > .1 for ATP versus SNP). In contrast to animal data, high dosages of intra-arterially infused ATP (up to 1000 micrograms.100 mL forearm-1.min-1) did not reveal a reduction in the forearm vasodilator response but appeared to be similar to the maximal forearm vasodilation as observed during postocclusive reactive hyperemia. CONCLUSIONS: These observations indicate that ATP induces a potent dose-dependent vasodilator response that is not mediated by P1-purinergic receptor stimulation or by the release of nitric oxide. Moreover, in healthy volunteers, the vasodilator response to high intra-arterial dosages of ATP is not reduced by the release of endothelium-derived contracting factors or by the stimulation of P2x-purinergic receptors on the smooth muscle cells.

Adenosine Triphosphate↗
PubMed1994

24-hour ambulatory blood pressure monitoring and spirapril in mild to severe essential hypertension: a randomized dose comparison.

This was a multicentre randomized, double-blind, parallel-group study to compare the antihypertensive efficacy of spirapril at 3 mg with 12 mg once daily, as determined by 24-hour ambulatory blood pressure monitoring (ABPM), in patients with mild to severe essential hypertension. Following a 4-week placebo run-in phase, 52 male and female outpatients, aged 23-67 years with mild to severe essential hypertension [diastolic blood pressure (DBP) > or = 100 mmHg and < 120 mmHg] were randomized to receive spirapril at either 3 mg or 12 mg once daily for 8 weeks. At the end of active treatment and using the standard mercury sphygmomanometer, the number of responders (sitting DBP < 90 mmHg, but decrease > or = 10 mmHg) was the same in both groups (32% and 37%). There were mean decrease in both systolic blood pressure (SBP) and DBP at trough with both 3 mg and 12 mg doses: -9/-7 mmHg and -12/-7 mmHg, respectively. The rate of normalization (trough DBP < or = 90 mmHg) was 12% and 30% with the 3 mg and 12 mg doses, respectively. Of the 44 patients whose daytime ABPM could be compared, one of 20 patients taking 3 mg of spirapril, and 9 of 24 taking 12 mg of spirapril achieved a DBP < or = 90 mmHg for all time intervals while awake. The differences in blood pressure-lowering were significant with both SBP and DBP during the day and at the end of the dosing interval (p < 0.001 and p < 0.01, respectively). The changes from baseline at 24 hours postdose for SBP/DBP were -3/-6 mmHg with 3 mg and -14/-12 mmHg with 12 mg of spirapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Endothelium and the regulation of vascular tone with emphasis on the role of nitric oxide. Physiology, pathophysiology and clinical implications.

After the discovery by Furchgott and colleagues in 1980 that the endothelium plays an obligatory role in acetylcholine-induced vasodilation many investigators have elucidated the role of the endothelium in the regulation of vascular tone. While the sympathetic nervous system serves the organism as a whole, the endothelium appears to act as a local regulator adapting blood flow to local metabolic needs. A variety of endothelium-derived relaxing and contracting factors such as nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor, endothelin and thromboxane A2 play a role in the endothelium-dependent control of vascular tone. Furthermore, nitric oxide inhibits thrombocyte aggregation and adhesion. Many diseases have been reported to be associated with an impaired endothelium-dependent vasodilation which may contribute to an increased susceptibility to vasospasm, decreased inhibition of thrombus formation and an impaired ability to reduce vascular resistance in ischaemic conditions. In hypertension, hypercholesterolaemia and diabetes mellitus this impairment may be interpreted as an early marker of a process that ultimately will lead to atherosclerosis. The impaired endothelium-dependent vasodilation probably contributes to the increased peripheral vascular resistance in hypertension and heart failure. The role of the endothelium does not seem to be restricted to cardiovascular diseases. Several mediators of inflammation stimulate the endothelium to release nitric oxide, suggesting an important role of the endothelium in the haemodynamic sequelae of sepsis.

Cardiovascular Diseases↗
PubMed1993

Reproducibility of the finger cooling test.

A finger cooling test is used to objectify Raynaud's phenomenon and to assess its severity. For this purpose, finger skin temperature (FST) and laser Doppler flux (LDF) are measured on the fingertips before and during cooling of the hand (16 degrees water bath for 5 min) and a subsequent recovery period (20 min). To study reproducibility, this test was performed twice within 3 months in 34 healthy subjects and in 56 Raynaud patients. Three test parameters were used in the analysis: the baseline value, the value after 12 min of recovery, and the mean level during recovery. We determined the limits of agreement (mean differences between the first and the second test +/- 2SD) and the coefficients of variation. No systematic differences between the first and the second test were found. Outside temperature did not influence FST or LDF. FST was shown to have a better reproducibility than LDF. For the baseline value in the total group the coefficient of variation was 3.3% for FST and, rather high, 21.6% for LDF. The limits of agreement for the baseline value in the total group were -4.8 to 4.2 degrees for FST and -25.2 to 22.2 arbitrary units for LDF. In conclusion, the applied cooling test has limited value in individual cases, but can be useful when comparing large groups in pathophysiologic or therapeutic studies.

Adult↗