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Biomedical subjects

L Linder

Publications and source records attributed to L Linder.

At least 19 recordsLinked to original sources
PubMed2002

Effect of low doses of 5-methyltetrahydrofolate and folic acid on plasma homocysteine in healthy subjects with or without the 677C-->T polymorphism of methylenetetrahydrofolate reductase.

BACKGROUND: The 677C-->T polymorphism of methylenetetrahydrofolate reductase can lead to increased homocysteine. Moderate increases of homocysteine can be lowered by folic acid (0.4-10 mg day-1). This study compared the effect of folic acid with 5-methyltetrahydrofolate, the active form of folate generated by this reductase, on homocysteine levels in healthy subjects and whether this is influenced by the 677C-->T polymorphism. MATERIALS AND METHODS: Either 400 micrograms day-1 of [6RS] 5-methyltetrahydrofolate or 400 micrograms day-1 of folic acid were administered orally to 10 wild-type and 10 homozygous subjects. Total homocysteine and folate were determined before and after 3 and 7 weeks of treatment, and 24 weeks after stopping treatment. RESULTS: After 3 and 7 weeks of treatment with 5-methyltetrahydrofolate, homocysteine levels fell from 11.6 +/- 1.5 to 9.0 +/- 2.3 and 8.7 +/- 1.8 (P < 0.005) in wild-type subjects and from 16.9 +/- 6.8 to 12.3 +/- 4.3 and 11.6 +/- 4.4 mumol/L, mean +/- SD (P < 0.005) in homozygous subjects, proving biological availability of 5-methyltetrahydrofolate irrespective of the 677C-->T genotype. After folic acid for 3 and 7 weeks, values fell from 12.6 +/- 3.3 to 9.2 +/- 2.9 and 9.2 +/- 2.7 (P < 0.005) and from 15.6 +/- 4.9 to 11.7 +/- 3.9 and 9.1 +/- 2.4 mumol L-1, mean +/- SD (P < 0.005) in wild-type and homozygous subjects, respectively. Six months after stopping treatment, homocysteine levels remained lower than pretreatment levels, with statistical significance, only in homozygous subjects treated with 5-methyltetrahydrofolate (12.1 +/- 2.5 vs. 16.9 +/- 6.8, P < 0.01). CONCLUSIONS: 5-methyltetrahydrofolate showed comparable efficacy in reducing homocysteine as folic acid. A prolonged effect 6 months after ceasing treatment with 5-methyltetrahydrofolate in homozygous subjects represents a further phenotypic effect of the 677TT methylenetetrahydrofolate reductase genotype.

Adult↗
PubMed2001

Local effect of transdermal isosorbide dinitrate ointment on hand vein diameter.

OBJECTIVE: To assess the effect of topically applied isosorbide dinitrate (ISDN) ointment on superficial hand veins preconstricted with phenylephrine. METHODS: Using the hand vein compliance technique, venous diameter changes were measured in a double-blind, randomised, placebo-controlled cross-over trial in 12 healthy volunteers. During preconstriction with phenylephrine, placebo or ISDN ointment was administered to assess the dilator effect of transdermal ISDN. Finally a single i.v. dose of nitroglycerine was administered into the hand vein to assess the maximal venous response to organic nitrovasodilators. RESULTS: ISDN ointment (equivalent to 13.4 +/- 3.61 mg ISDN) caused a significant dilator effect of 39.1 +/- 21.7% (mean +/- SEM, P=0.02) which reached its maximum after 42.5 +/- 16.6 min. Maximum ISDN effects were inversely correlated with venous baseline diameter (r2=0.38, P=0.03) and independent of the amount of ointment applied or the extent of preconstriction (P > 0.3). CONCLUSION: Similar to nitroglycerine, topical ISDN may relax superficial hand veins within 60 min after application, suggesting that it might ease venepuncture particularly of small vessels. The large variability of the effect and the time to reach the effect, however, restrict its practical usefulness.

Administration, Cutaneous↗
PubMed2001

Measurement of immunoreactive angiotensin-(1-7) heptapeptide in human blood.

BACKGROUND: The renal enzyme renin cleaves from the hepatic alpha(2)-globulin angiotensinogen angiotensin-(1-10) decapeptide [Ang-(1-10)], which is further metabolized to smaller peptides that help maintain cardiovascular homeostasis. The Ang-(1-7) heptapeptide has been reported to have several physiological effects, including natriuresis, diuresis, vasodilation, and release of vasopressin and prostaglandins. METHODS: To investigate Ang-(1-7) in clinical settings, we developed a method to measure immunoreactive (ir-) Ang-(1-7) in 2 mL of human blood and to estimate plasma concentrations by correcting for the hematocrit. A sensitive and specific antiserum against Ang-(1-7) was raised in a rabbit. Human blood was collected in the presence of an inhibitor mixture including a renin inhibitor to prevent peptide generation in vitro. Ang-(1-7) was extracted into ethanol and purified on phenylsilylsilica. The peptide was quantified by radioimmunoassay. Increasing doses of Ang-(1-7) were infused into volunteers, and plasma concentrations of the peptide were measured. RESULTS: The detection limit for plasma ir-Ang-(1-7) was 1 pmol/L. CVs for high and low blood concentrations were 4% and 20%, respectively, and between-assay CVs were 8% and 13%, respectively. Reference values for human plasma concentrations of ir-Ang-(1-7) were 1.0-9.5 pmol/L (median, 4.7 pmol/L) and increased linearly during infusion of increasing doses of Ang-(1-7). CONCLUSIONS: Reliable measurement of plasma ir-Ang-(1-7) is achieved with efficient inhibition of enzymes that generate or metabolize Ang-(1-7) after blood sampling, extraction in ethanol, and purification on phenylsilylsilica, and by use of a specific antiserum.

Adult↗
PubMed2000

Correlation between apolipoprotein B and endothelin-1-induced vasoconstriction in humans.

Low-density lipoprotein (LDL) concentrations have been linked to altered responses to endogenous vasodilators and vasoconstrictors. We evaluated retrospectively the relationship between LDL and vasoconstrictor (endothelin-1, phenylephrine) responsiveness of the forearm vasculature in 15 elderly healthy volunteers with apolipoprotein B and LDL levels in the normal range. In contrast to phenylephrine, changes in forearm vascular resistance induced by endothelin-1 were correlated with apolipoprotein B, LDL, and total cholesterol concentrations in women but not in men. These findings might suggest that lipids may increase vascular tone through both impaired endothelial vasodilation and increased vasoconstriction to endothelin-1 at least in women.

Aged↗
PubMed2000

Auditory and electroencephalographic effects of midazolam and alpha-hydroxy-midazolam in healthy subjects.

AIMS: Whereas cortical EEG effects of benzodiazepines are well characterized, information about benzodiazepine effects in other areas of the central nervous system is sparse. This study investigated the action of midazolam and its active metabolite alpha-hydroxy-midazolam on different parts of the auditory pathway in six healthy volunteers in a randomized, double-blind, three-way cross-over study. METHODS: Acoustically evoked short (SLP) and middle (MLP) latency potentials, transitory evoked otoacoustic emissions (TEOAE), and EEG power spectra were analysed after short i. v. injections of placebo, or 0.15 mg kg-1 midazolam, or alpha-hydroxy-midazolam, respectively. RESULTS: All subjects fell asleep during the 4 min infusion of active drug. SLP showed a significant transient increase of Jewett wave V 10 min after injection for midazolam and alpha-hydroxy-midazolam while the latency of wave I was unchanged. Both benzodiazepines induced a marked and long-lasting MLP amplitude decrease for 240 min with slow recovery over the following 360 min. No changes of TEOAE were observed. In agreement with earlier reports, increases in EEG beta activity and decreases in alpha activity were observed after administration of either drug. CONCLUSIONS: Systemically administered benzodiazepines modulate the auditory pathway above the level of the cochlea. While SLP changes were closely associated with sedation and high plasma benzodiazepine concentrations, MLP effects persisted for hours after sedation even at low benzodiazepine plasma levels. Evoked potentials may therefore be more sensitive than EEG as a tool to monitor benzodiazepine effects.

Adult↗
PubMed2000

Cancellous impaction grafting in the human femur: histological and radiographic observations in 6 autopsy femurs and 8 biopsies.

6 whole postmortem femurs and 8 femoral biopsies were studied histologically, 3 months to 8 years after cancellous impaction grafting with a cemented stem for aseptic loosening. All stems were stable. Radiographs showed cortical healing in 5 cases, trabecular remodelling in 1, and trabecular incorporation in 9. There was a radiolucent line in 1 case. The histology varied. There was always a viable cortical shell around the grafted area. 1 patient showed complete bony restitution. The others still had varying amounts of remaining graft in the neo-medullary cavity, even after 8 years. The graft particles were usually embedded in dense fibrous tissue, thus forming a supporting composite tissue capable of carrying load. There was no time-dependent deterioration in the histological appearance. Radiographically, cortical healing and trabecular remodeling corresponded to viable bone. The lack of a radiolucent line said little about the viability of the tissue closest to the cement. The radiographs did not detect thin soft tissue membranes. Radiographic criteria used to assess primary total joint replacement do not necessarily apply to impaction grafting, and radiographic changes should be interpreted cautiously, especially as regards tissue viability.

Aged↗
PubMed1999

Neurokinin-1 receptor antagonist R116301 inhibits substance P-induced venodilation.

OBJECTIVE: To test the effect of the neurokinin-1 receptor antagonist hydroxybutanedioate (R116301) in human hand veins in vivo. METHODS: In a randomized, double-blind, placebo-controlled crossover study we used the hand vein compliance method to evaluate the inhibition of the response to substance P by R116301. RESULTS: In hand veins preconstricted with phenylephrine to 21% +/- 2.6% (mean +/- SEM, placebo) and 25% +/- 3.0% (R116301) of the initial diameter, substance P resulted in a mean venodilation of 84% +/- 7% and 87% +/- 13% (P = .8) before administration of placebo and R116301, respectively. Oral administration of 300 mg R116301 resulted in peak plasma concentrations of 1.16 +/- 0.1 microg/mL within 128 +/- 14 minutes. With increasing R116301 plasma concentrations, substance P-induced venodilation decreased significantly (P < .001), whereas placebo had no effect. Mean substance P-induced venodilation was markedly reduced to 8% +/- 7%. CONCLUSION: This study confirms the presence of neurokinin-1 receptors in human veins and the effectiveness of the neurokinin-1 receptor antagonist R116301 in human hand veins.

Administration, Oral↗
PubMed1999

Pharmacokinetics and pharmacodynamics of clomethiazole after oral and rectal administration in healthy subjects.

Clomethiazole, a sedative-hypnotic and anticonvulsant drug, has been successfully administered orally and intravenously, but in cases where either of these methods presents complications, rectal administration may represent a practical alternative. We sought to compare the single-dose pharmacokinetics and pharmacodynamics of clomethiazole after oral and rectal administration. Ten healthy adult volunteers were given 600 mg clomethiazole edisylate (corresponding to 390 mg clomethiazole base) in 2 capsules as a single oral or rectal dose in a double-masked, double-dummy, crossover fashion. Serum concentrations were measured up to 10 hours after administration using a specific high-performance liquid chromatography method. Computerized reaction-time measurement and visual analogue scales (VAS) were used to assess drug effects. Peak serum concentrations were significantly higher after oral administration (mean +/- SEM, oral 1.76 +/- 0.47 microg/mL vs rectal 0.48 +/- 0.14 microg/mL; P = 0.03) and appeared earlier (55 +/- 12 vs 89 +/- 11 min; P = 0.04). Area under the concentration-time curve values were similar after administration by both routes (oral 116 +/- 20.6 vs rectal 105 +/- 36.0 microg x min/mL), with a relative rectal bioavailability of 90% compared with oral administration. The objective pharmacodynamic effects on reaction time (increase of 104 +/- 26 vs 66 +/- 22 ms, oral vs rectal) and working speed (decrease of 132 +/- 38 vs 97 +/- 32 ms, oral vs rectal) were not significantly different. Subjective pharmacodynamic effects, as measured on the VAS, were comparable with both routes of administration. Clomethiazole was well tolerated, with a similar adverse effect profile for both routes of administration. The effects of rectal dosing of clomethiazole were similar to those of oral dosing but appeared to occur later. Our results suggest that rectal administration of a single 600-mg clomethiazole edisylate dose bears no safety risk. Therefore, rectal administration could be considered when neither oral nor parenteral administration is possible and a later onset of effect is not critical.

Administration, Oral↗
PubMed1998

Histology of the femur after cancellous impaction grafting using a Charnley prosthesis.

We report the histologic findings of a retrieved femur 6 months after a cemented hip revision with a Charnley standard prosthesis and impaction of morselized allograft. Most transplanted areas were revascularised. In the proximal femur there was new bone formation peripherally, but a substantial amount of fibrous stroma embedding graft pieces closer to the cement. In the diaphysis new bone formation had proceeded to within less than 0.5 mm of the cement.

Aged↗
PubMed1997

Inverse correlation between endothelin-1-induced peripheral microvascular vasoconstriction and blood pressure in glaucoma patients.

BACKGROUND: The potent vasoconstrictor peptide endothelin-1 has been shown to participate in the control of peripheral vascular tone and in the regulation of ocular perfusion. In glaucoma patients vasospasms and arterial hypotension have been identified as risk factors for the progression of glaucomatous damage, and the regulation of endothelin-1 release is disturbed in some of these patients. The aim of this study was to assess the relationship between resting blood pressure and cutaneous vascular responsiveness to endothelin-1 and phenylephrine in patients with glaucoma and in matched controls. METHODS: In 9 patients with primary open-angle glaucoma (POAG), 7 patients with normal tension glaucoma (NTG), and 16 age- and sex-matched controls, endothelin-1 and phenylephrine responses were assessed in the human forearm microcirculation using laser Doppler flowmetry during intra-arterial drug administration. Blood pressure was measured intra-arterially. RESULTS: In contrast to alpha 1-adrenergic effects, endothelin-1 responses were inversely correlated to both systolic (r2 = 0.27, P = 0.05) and diastolic (r2 = 0.54, P = 0.001) blood pressure in glaucoma patients, whereas there was no such correlation in controls. Patients with lower blood pressure values were more sensitive to the vasoconstrictor effects of endothelin-1. Cutaneous responsiveness to endothelin-1 and phenylephrine was similar in glaucoma patients and in controls. CONCLUSION: These results reveal that glaucoma patients appear to have peripheral microvascular abnormalities which are exhibited as altered responsiveness to endothelin-1. Thus, this study supports the hypothesis that endothelin-1-related microvascular dysfunction may be involved in the pathogenesis of glaucomatous damage.

Adult↗
PubMed1997

Quinaprilat induces arterial vasodilation mediated by nitric oxide in humans.

The beneficial therapeutic effects of angiotensin-converting enzyme (ACE) inhibitors are the result of reduced angiotensin II formation and possibly also of an accumulation of bradykinin that is inactivated by ACE. In particular, recently developed ACE inhibitors with tissue-penetrating properties, such as quinaprilat, may exert vascular effects via the bradykinin B2-receptor. To test direct arterial effects of quinaprilat and enalaprilat and to study their effects on vasodilation induced by bradykinin, venous occlusion plethysmography was used during local intra-arterial drug administration into the brachial artery in healthy volunteers. The response to bradykinin was augmented by both ACE inhibitors, but the effect of quinaprilat (3.9 nmol/min) was exclusively attributable to its direct vasodilator action. Enalaprilat (13 nmol/min) did not change baseline blood flow in the human forearm circulation. In contrast, quinaprilat significantly increased arterial flow from 3.5 +/- 0.5 to 4.6 +/- 0.7 mL/100 mL tissue/min, which was inhibited by N(G)-monomethyl-L-arginine (8 micromol/min IA). Moreover, the effect of sodium nitroprusside (0.023 to 22.9 nmol/min) was substantially attenuated during concomitant administration of quinaprilat. These results suggest that quinaprilat induces vascular effects beyond the inhibition of angiotensin II formation; it causes vasodilation by increasing vascular nitric oxide production and thereby attenuates the relaxing effect of the nitric oxide donor sodium nitroprusside.

Adult↗
PubMed1997

Role of nitric oxide in the regulation of the mechanical properties of peripheral conduit arteries in humans.

Whether nitric oxide (NO) contributes to the regulation of the mechanical properties of large arteries in humans is not known. We measured the effect of local administration of the inhibitor of NO synthesis N(G)-monomethyl-L-arginine (L-NMMA; 1 and 4 micromol x L[-1] x min[-1] for 5 minutes) and acetylcholine (3 and 30 nmol x L[-1] x min[-1] for 3 minutes) on radial artery diameter and wall thickness in 11 healthy volunteers using an echo-tracking system coupled to a measurement of radial blood flow (Doppler) and arterial pressure. At the highest dose, L-NMMA reduced radial blood flow but surprisingly decreased incremental elastic modulus (from 1.36+/-0.22 to 1.00+/-0.22 kPa x 10[3]; P<.05) and increased arterial compliance (from 3.20+/-0.46 to 4.07+/-0.45 m2 x kPa x 10(-8), P<.05), without affecting radial artery internal diameter, wall thickness or midwall stress, thus reflecting a decrease in vascular tone. Acetylcholine decreased incremental elastic modulus (from 1.27+/-0.08 to 0.88+/-0.07 kPa x 10[3]; P<.05) and increased arterial diameter, radial blood flow, and compliance (from 2.82+/-0.16 to 5.30+/-0.62m2 x kPa x 10[-8]; P<.05). These results demonstrate in vivo that NO is involved in the regulation of the mechanical properties of large arteries in humans. However, the effects of L-NMMA, ie, a decrease in arterial wall rigidity and an increase in arterial compliance, which occur in the absence of any changes in blood pressure or arterial geometry, suggest that inhibition of NO synthesis is associated in humans with a paradoxical isometric smooth muscle relaxation. This effect could be due to the development of compensatory vasodilating mechanisms after NO synthesis inhibition.

Acetylcholine↗
PubMed1996

Substance P in human hand veins in vivo: tolerance, efficacy, potency, and mechanism of venodilator action.

OBJECTIVES: To study potency, efficacy, development of tolerance, and mechanism of action of substance P, an endothelium-dependent vasodilator neurokinin, in human hand veins in vivo. METHODS: Thirty-three healthy subjects were studied with use of the hand vein compliance technique. In hand veins preconstricted with the alpha 1-agonist phenylephrine, substance P and antagonists of nitric oxide formation (L-NG-mono-methyl-arginine, L-NMMA), adenosine triphosphate (ATP)-dependent potassium channels (glyburide), angiotensin converting enzyme (enalaprilat), and cyclooxygenase (acetylsalicylic acid) were infused and the venodilator effect was measured. RESULTS: Substance P proved to be the most potent venodilator known thus far (the dose-rate exerting 50% of mean maximum dilation [ED50], geometric mean: 0.105 pmol/min). Rapid development of tolerance occurred in seven of eight volunteers studied. Glyburide decreased the venodilator action of a single dose of substance P (1.5 pmol/min) from 81% to 28% of baseline venodilation (p < 0.05), suggesting that substance P acts through release of endothelium-derived hyperpolarizing factor. The cyclooxygenase-inhibitor acetylsalicylic acid reduced substance P-induced venodilation from 53% +/- 7% to 34% +/- 8% (p < 0.05), whereas L-NMMA had no effect. CONCLUSIONS: Unlike in other vessels, substance P-induced venodilation in hand veins is not mediated through nitric oxide but to a significant extent through a glyburide-sensitive pathway. Therefore it appears likely that substance P activates ATP-dependent potassium channels on vascular smooth muscle cells through the release of endothelium-derived hyperpolarizing factor.

Adult↗
PubMed1996

Effects of cilazapril on vascular structure and function in essential hypertension.

Hypertension is associated with an altered design of resistance vessels and decreased endothelium-dependent vasodilator response to acetylcholine. A role of angiotensin II in both defects is suggested by animal experiments in which angiotensin-converting enzyme inhibition reverted structural and functional changes. We investigated the effects of 20 weeks of therapy with the angiotensin-converting enzyme inhibitor cilazapril (5 mg twice daily) on the endothelium-dependent response to brachial artery infusions of acetylcholine and the endothelium-independent vascular relaxation after sodium nitroprusside in 22 subjects with mild to moderate essential hypertension. In addition, we measured minimal forearm vascular resistance (ratio of mean arterial pressure and forearm blood flow after heating, ischemia, and ischemic exercise) as an indirect estimate of vascular structure. Cilazapril decreased blood pressure (151 +/- 14/99 +/- 7 mm Hg during placebo to 138 +/- 17/89 +/- 8 mm Hg after cilazapril treatment, P<.01) and baseline (42.2 +/- 12.6 to 37.1 +/- 10.6 U, P<.05) and minimal (3.0 +/- 1.1 to 2.4 +/- 0.7 U, 15.9 +/- 20.2%; P<.05) forearm vascular resistances. The change in minimal forearm vascular resistance was unrelated to age, duration of hypertension, or changes in blood pressure. Sodium nitroprusside increased forearm blood flow from 2.6 +/- 1.0 to 11.4 +/- 5.9 mL/min per 100 mL and acetylcholine to 21.5 +/- 17.8. Both responses did not change after cilazapril. The data provide indirect evidence that cilazapril therapy may improve vascular structure in human hypertension. The lack of relationship between vascular and blood pressure changes would be compatible with experimental evidence supporting a role for angiotensin II in the development and regression of vascular changes, but this needs further study. Therapy with cilazapril for 20 weeks, like other antihypertensive therapy, does not seem to influence endothelial vasodilator function in humans to a significant degree.

Adult↗
PubMed1996

Subconstrictor doses of neuropeptide Y potentiate alpha 1-adrenergic venoconstriction in vivo.

The 36-amino acid human neuropeptide Y is a vasoactive compound released after stimulation of the sympathetic nervous system. In addition to its direct and long-lasting vasopressor effects, it may potentiate the constrictor action of catecholamines and other vasoconstrictors at doses that do not per se exert vascular effects. Using the hand vein compliance technique, we have previously shown that neuropeptide Y also constricts superficial hand veins and that its effects may last for several hours. In this study, we investigated the local effect of neuropeptide Y on alpha 1-adrenergic venoconstriction in nine healthy volunteers at dose rates that did not affect venous compliance. On separate days, cumulative dose-response curves to phenylephrine alone and with coadministration of 1 or 30 pmol neuropeptide Y per minute were constructed, and the responses were fitted to a four-parameter logistic equation. Neuropeptide Y dose dependently shifted the phenylephrine curves toward lower dose rates without affecting maximal effects. ED50 values for phenylephrine alone and with 1 or 30 pmol/min neuropeptide Y were 4.0, 4.9 (P = NS versus control), and 1.2 (P < .005) nmol/min, respectively. Comparison with neuropeptide Y dose-response curves revealed that the interaction was synergistic. These are the first data in humans to show that small dose rates of neuropeptide Y may potentiate alpha-adrenergic effects in vivo. Because this interaction occurs at estimated local concentrations nearly achieved in humans, these studies suggest that neuropeptide Y might modulate the filling of this capacitance system in vivo.

Adrenergic alpha-Agonists↗
PubMed1995

Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo.

BACKGROUND: Experimental evidence suggests that flow-dependent dilatation of conduit arteries is mediated by nitric oxide (NO) and/or prostacyclin. The present study was designed to assess whether NO or prostacyclin also contributes to flow-dependent dilatation of conduit arteries in humans. METHODS AND RESULTS: Radial artery internal diameter (ID) was measured continuously in 16 healthy volunteers (age, 24 +/- 1 years) with a transcutaneous A-mode echo-tracking system coupled to a Doppler device for the measurement of radial blood flow. In 8 subjects, a catheter was inserted into the brachial artery for measurement of arterial pressure and infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 8 mumol/min for 7 minutes; infusion rate, 0.8 mL/min). Flow-dependent dilatation was evaluated before and after L-NMMA or aspirin as the response of the radial artery to an acute increase in flow (reactive hyperemia after a 3-minute cuff wrist occlusion). Under control conditions, release of the occlusion induced a marked increase in radial blood flow (from 24 +/- 3 to 73 +/- 11 mL/min; P < .01) followed by a delayed increase in radial diameter (flow-mediated dilatation; from 2.67 +/- 0.10 to 2.77 +/- 0.12 mm; P < .01) without any change in heart rate or arterial pressure. L-NMMA decreased basal forearm blood flow (from 24 +/- 3 to 13 +/- 3 mL/min; P < .05) without affecting basal radial artery diameter, heart rate, or arterial pressure, whereas aspirin (1 g PO) was without any hemodynamic effect. In the presence of L-NMMA, the peak flow response during hyperemia was not affected (76 +/- 12 mL/min), but the duration of the hyperemic response was markedly reduced, and the flow-dependent dilatation of the radial artery was abolished and converted to a vasoconstriction (from 2.62 +/- 0.11 to 2.55 +/- 0.11 mm; P < .01). In contrast, aspirin did not affect the hyperemic response nor the flow-dependent dilatation of the radial artery. CONCLUSIONS: The present investigation demonstrates that NO, but not prostacyclin, is essential for flow-mediated dilatation of large human arteries. Hence, this response can be used as a test for the L-arginine/NO pathway in clinical studies.

Adult↗