Large Human Arteries Research Articles

CD40 Co-Stimulatory Molecule Expression by Dendritic Cells in Primary Atherosclerotic Lesions in Carotid Arteries and in Stenotic Saphenous Vein Coronary Artery Grafts

We have previously identified dendritic cells in the intima of human large arteries and stenotic vein coronary bypass grafts. The mechanisms by which these dendritic cells might regulate immune responses in atherosclerotic lesions and stenotic vein grafts are unknown. The aim of the present study was to investigate whether dendritic cells in carotid plaques and in stenotic aortocoronary vein grafts express an immunoregulatory molecule CD40. Segments of wall from eight carotid arteries and three stenotic aortocoronary saphenous vein grafts were obtained at operation. CD40+ cells were detected in all specimens of both occluded and stenotic grafts and carotid plaques. Although CD40+ cells of various cell types were intermingled in most areas within the plaques and stenotic grafts, there were sites where CD40+ cells were located in small groups. Consecutive sections demonstrated that a small population of CD40+ cells stained positively for S100. These CD40+/S100+ cells were clustered within the intima but were also found in the media and adventitia. This suggests that dendritic cells, which accumulate within vessels affected by atherosclerosis and graft disease, express CD40 co-stimulatory molecule. The expression of CD40 molecule on the dendritic cells may be important in regulating T cell responses within atherosclerotic plaques and stenotic vein grafts.

CD40 co-stimulatory molecule expression by dendritic cells in primary atherosclerotic lesions in carotid arteries and in stenotic saphenous vein coronary artery grafts

We have previously identified dendritic cells in the intima of human large arteries and stenotic vein coronary bypass grafts. The mechanisms by which these dendritic cells might regulate immune responses in atherosclerotic lesions and stenotic vein grafts are unknown. The aim of the present study was to investigate whether dendritic cells in carotid plaques and in stenotic aortocoronary vein grafts express an immunoregulatory molecule CD40. Segments of wall from eight carotid arteries and three stenotic aortocoronary saphenous vein grafts were obtained at operation. CD40 + cells were detected in all specimens of both occluded and stenotic grafts and carotid plaques. Although CD40 + cells of various cell types were intermingled in most areas within the plaques and stenotic grafts, there were sites where CD40 + cells were located in small groups. Consecutive sections demonstrated that a small population of CD40 + cells stained positively for S100. These CD40 +/S100 + cells were clustered within the intima but were also found in the media and adventitia. This suggests that dendritic cells, which accumulate within vessels affected by atherosclerosis and graft disease, express CD40 co-stimulatory molecule. The expression of CD40 molecule on the dendritic cells may be important in regulating T cell responses within atherosclerotic plaques and stenotic vein grafts.

Effect of hypertension on viscoelasticity of large arteries in humans.

Two traditional methodologic approaches, the analysis of the arterial pressure waveform in the time domain and the measurement of pulse wave velocity along the arterial tree, have been extensively used to determine the distensibility of large arteries in humans. They have shown that large artery walls are stiffened in the presence of hypertension. However, several methodologic limitations, especially the incapability of these methods to take into account the physiologic pressure-dependence of arterial distensibility, have led to the development of new approaches for characterizing more in depth the elastic and viscous properties of large arteries. The noninvasive recording of instantaneous pressure and diameter waveforms in superficial arteries (carotid or femoral) by means of tonometry and ultrasonography allows, via appropriate model of the arterial wall, determination of the pure elastic properties as well as the wall viscosity of the vessel. Using case (hypertensive)-control (normotensive) studies it has been found that elastic alteration (stiffening) was preferential in the femoral artery rather than in the carotid artery and that viscous alteration (increased wall viscosity) was relatively uniform in both arteries. This topographic dissociation between elastic and viscous responses of the arterial wall to hypertension suggests that the elastic alteration might be a local phenomena dependent on the singularities of the arterial system, whereas abnormal wall viscosity may reflect a more general influence of hypertension on large artery smooth muscle, the likely determinant factor of viscosity. Therefore, the elastic and viscous components of the arterial walls should be considered independently when assessing the development of hypertensive vascular change and its response to antihypertensive treatment.

Source of calcium for contractile responses of large and small human intramyometrial arteries.

The role of calcium (Ca(2+)) released from intracellular stores and the entry of extracellular Ca(2+) for vasopressin (AVP)-induced responses in large and small, human, intramyometrial arteries was investigated. There was no statistical difference as revealed by pD(2) values (-log EC(50)), in the sensitivity of large and small vessels to AVP. Nimodipine caused an inhibition of contractions induced by low concentrations (10(-10) mol/l) of AVP in both types of vessels but, at higher concentration (>10(-10) mol/l), whereas responses in small arteries were diminished, in large arteries they remained unchanged. In Ca(2+)-free solution, responses of large and small arteries to potassium and to 10(-10) mol/l AVP were abolished. With 10(-6) mol/l AVP, response in small arteries was completely inhibited, whereas in large arteries it was reduced by approximately 50%. Additional experiments were done on large arteries. Thapsigargin (TSG), which causes depletion of internal Ca(2+) stores, caused a significant reduction in responses. Following treatment with TSG, responses to AVP in Ca(2+)-free solution were almost completely inhibited but arteries responded again when incubated in normal physiological salt solution. The results indicate that in contrast to large arteries, small arteries are highly dependent on extracellular Ca(2+). Response of large arteries showed considerable dependence on Ca(2+) stored internally particularly, for maximum activation.

Evidence for tetrodotoxin-sensitive sodium currents in primary cultured myocytes from human, pig and rabbit arteries

Primary cultured human coronary myocytes express a tetrodotoxin-sensitive sodium current (I(Na)). Here, we have investigated whether I(Na) is expressed in vascular smooth muscles cells (VSMCs) isolated from other large arteries, and other mammals. VSMCs were enzymatically dissociated, kept in primary culture, and macroscopic I(Na) was recorded using the whole-cell patch-clamp technique. We found that I(Na) is expressed in VSMCs grown from human aortic (90%; n=50) and pulmonary (44%; n=19) arteries, and in the human aortic myocyte cell line HAVSMC (94%; n=27). I(Na) was also detected in pig coronary (60%; n=33), and rabbit aortic (47%; n=15), but not in rat aortic VSMCs (n=20). These different I(Na) had similar voltage thresholds for activation (approximately equal to -50 mV), and were highly sensitive to extracellularly applied tetrodotoxin. We conclude that I(Na) is expressed in VSMCs grown from various types of large arteries in humans, pig and rabbit.

Association of remnant lipoprotein levels with impairment of endothelium-dependent vasomotor function in human coronary arteries.

It remains undetermined whether triglyceride-rich lipoproteins are an independent risk factor for atherosclerosis. The correlation of responses of coronary arterial diameter (quantitative coronary angiography) and coronary blood flow (intracoronary flow wire technique) to intracoronary infusion of acetylcholine (10 and 50 microg/min) with coronary risk factors including remnant lipoprotein levels was statistically analyzed in 106 consecutive subjects with normal coronary angiograms. Remnant lipoproteins were isolated from fasting blood with an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-1 and anti-apoB-100 monoclonal antibodies. In multivariate stepwise regression analysis, remnant lipoprotein levels had the most significant correlation with abnormal epicardial coronary vasomotor responses to acetylcholine infusion, reflected by impaired dilation or constriction of the epicardial coronary arteries, and the levels also had an inverse and independent correlation with the coronary blood flow increase in response to acetylcholine. In a subgroup of 53 consecutive subjects, constrictor responses of epicardial coronary diameters to intracoronary infusion of NG-monomethyl-L-arginine (50 micromol/min for 4 minutes) at baseline, reflecting the presence of coronary nitric oxide bioactivity, had an inverse and independent correlation with remnant lipoprotein levels by use of multivariate analysis. Remnant lipoprotein levels were independently associated with abnormal endothelium-dependent vasomotor function in large and resistance coronary arteries in humans, indicating that remnant lipoproteins may impair endothelial vasomotor function in human coronary arteries. The decrease in coronary nitric oxide bioactivity may be responsible in part for the inhibitory effects of remnant lipoproteins.

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.

Arterial stiffening: opposing effects of age- and hypertension-associated structural changes

This article reviews the effects of aging and hypertension on geometrical (lumen and arterial wall thickness) and functional (distensibility) properties of large and medium-sized arteries in humans. Several clinical and animal studies show that arterial wall hypertrophy does not increase the elastic modulus of the arterial wall material during sustained essential hypertension. The structural changes associated with either hypertension or aging have opposing effects on arterial distensibility, under similar transmural conditions: the former increasing it, the latter decreasing it. Thus, hypertension cannot be assimilated to aging. The structural and functional changes of the arterial wall material that are associated with the hypertension-induced hypertrophy could be a means by which medium-sized arteries maintain their distensibility characteristics despite increased distending pressure, and large arteries compensate for the age-induced decrease in arterial compliance.

Participation of 5-HT1-like and 5-HT2A receptors in the contraction of human temporal artery by 5-hydroxytryptamine and related drugs.

1. We investigated the hypothesis that, as in some other large human arteries, 5-HT-induced contraction of the temporal artery is mediated through two co-existing receptor populations, 5-HT1-like- and 5-HT2A. Temporal arterial segments were obtained from patients undergoing brain surgery and rings prepared set up to contract with 5-HT and related agents. Fractions of maximal 5-HT responses mediated through 5-HT1-like and 5-HT2A receptors, f1 and f2 = 1-f1, were estimated by use of the 5-HT2A-selective antagonist ketanserin. 2. In rings with intact endothelium 5-HT evoked contractions with a -log EC50, M of 7.0. Ketanserin (10-1000 nM) antagonized part of the 5-HT-induced contractions. Ketanserin-resistant components of 5-HT-induced contractions were found with -log EC50, M of 6.9 and f1 of 0.17 (100 nM ketanserin) and -log EC50, M of 6.4 and f1 of 0.20 (1000 nM ketanserin). 3. In rings with endothelial function attenuated by enzymatic treatment, 5-HT caused contractions with a -log EC50, M of 7.2 that were partially blocked by ketanserin. Ketanserin-resistant components of 5-HT-induced contractions were found with -log EC50, M 7.4 and f1 of 0.16 (100 nM ketanserin) and -log EC50, M of 7.5 and f1 of 0.14 (1000 nM ketanserin). 4. The ketanserin-resistant component of 5-HT-evoked contraction was blocked by methiothepin (100-1000 nM) consistent with mediation through 5-HT1-like receptors. 5. In rings with intact endothelium the 5-HT1-like-selective agonist, sumatriptan, caused small contractions with a -log EC50, M of 6.5 and intrinsic activity of 0.21 with respect to 5-HT that were resistant to blockade by 1000 nM ketanserin but antagonized by 100 nM methiothepin. 6. In rings with intact endothelium the 5-HT2A receptor partial agonist SK&F 103829 (2,3,4,5-tetrahydro-8[methyl sulphonyl]-1H3-benzazepin-7-ol methensulphonate) contracted rings with a -log EC50, M of 5.0 and an intrinsic activity of 0.49 with respect to 5-HT; the effects were antagonized by ketanserin 1000 nM. 7. We conclude that 80-86% of the maximum 5-HT-evoked contraction of human temporal artery is mediated through 5-HT2A receptors, the remainder through 5-HT1-like-receptors, regardless of whether or not endothelium is functional. The 5-HT1-like-receptors are more likely to be 5-HT1D beta receptors than 5-HT1D alpha receptors and sumatriptan is a full agonist for these receptors. As found in arteries of other species, SK&F 103829 is a partial agonist for 5-HT2A receptors of human temporal artery.

Nitric Oxide Is Responsible for Flow-Dependent Dilatation of Human Peripheral Conduit Arteries In Vivo

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. 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. 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.

Transcranial doppler sonography during isoflurane/N2O anaesthesia and surgery: flow velocity, “vessel area” and “volume flow”

Transcranial Doppler sonography (TCD) constitutes an advance in noninvasive monitoring of the cerebral circulation. However, as long as the diameter and cross-sectional area of the insonated middle cerebral artery (MCA) remain unknown, the derived flow velocities (v) are not informative. It is not known how the human MCA is influenced by anaesthetic agents. However, a TCD-modification allows noninvasive determination of "vessel area" (VA) and "volume flow" (VF) in MCA by analysing the backscattered Doppler power. This investigation evaluates the effects of isoflurane (in combination with N2O and surgery) on v, VA and VF. In 14 patients (ASA I) scheduled for minor surgical or gynaecological operations, anaesthesia was induced with droperidol, alfentanil, thiopentone and vecuronium. After intubation ventilation with N2O:O2 = 3:2 was adjusted, to maintain endexpiratory carbon dioxide (FECO2) constant between 4 and 5%. Baseline values of heart rate (HR), oscillometric mean arterial pressure (MAP), and TCD variables (v, VA VF) were measured before adding 2.4% isoflurane to the inspiratory mixture. Further measurements-were made 3, 6, 10, and 20 min after starting isoflurane. Surgery commenced between the sixth and tenth minute after isoflurane application. The MAP, FECO2, and v showed only minor alterations; HR increased after 6, 10 and 20 min. Transcranial "vessel area" and "volume flow" showed increases after isoflurane inhalation. The increase of "vessel area" supports the assumption that isoflurane greater than 1 MAC dilates large human cerebral arteries, so that if flow velocities are considered alone, alterations of cerebral blood flow may easily be underestimated.

Comparative effects of diabetes mellitus and hypertension on physical properties of human large arteries

Objectives. The effects of hypertension and diabetes on the physical properties of large arteries were compared in men.Background. Although these two diseases are linked to vascular stiffening, no study has analyzed whether the arterial rigidity in diabetes is as substantial as in hypertension.Methods. Noninvasive measurements of brachial artery mean pressure, diameter (pulsed Doppler study) and compliance (pulse wave velocity) were obtained in 29 men: 11 control subjects, 9 hypertensive nondiabetic patients and 9 diabetic normotensive patients. Individual diameter- and compliance-pressure curves extrapolated from the measured diameter and mean pressure point with a logarithmic elastic model permitted calculation of isobaric diameter and compliance at the same pressure in each subject.Results. Compared with control subjects, hypertensive patients had a larger brachial artery measured diameter and isobaric diameter (p < 0.01) and lower measured and isobaric compliance (p < 0.001, p < 0.01). Compared with control subjects, diabetic patients had lower measured and isobaric compliance (p < 0.01). Comparison of diabetic and hypertensive patients showed that measured diameter and isobaric diameter were decreased in the former (p < 0.01). In the control and hypertensive groups, mean pressure correlated positively with measured diameter and isobaric diameter (p < 0.01) and negatively with measured and isobaric compliance (p < 0.001 and p < 0.01, respectively). In the control and diabetic groups, fasting glucose correlated negatively with measured and isobaric compliance (p < 0.01, p < 0.05).Conclusions, Intrinsic alterations of the large artery independent of a stretching pressure effect reduce arterial elasticity similarly in those with hypertension or diabetes. The loss of compliance is related to the chronic elevation of blood pressure in hypertension and to that of glycemia in diabetes and is associated with a relative large artery vasoconstriction in diabetic patients as compared with patients with hypertension.

Effect of perindopril on the development of atherosclerosis in the cholesterol-fed rabbit.

1. The aim of the study was to examine the effect of the angiotensin-converting enzyme inhibitor perindopril on the development of atheroma in the cholesterol-fed rabbit. 2. The normal human carotid artery, like most large human arteries, has a preformed diffuse intimal thickening. To model this thickening, the right carotid artery of the 12-week-old rabbit had an expanded balloon catheter passed down it to remove the endothelium and partially damage the media. 3. Fourteen weeks after this operation, a myointimal thickening similar in almost all respects to the human intimal thickening had developed. The rabbits were then divided into six groups of six rabbits fed on: (i) a 1% cholesterol diet; (ii) a 1% cholesterol diet plus a hypotensive dose of perindopril (0.3 mg/kg per day); (iii) a 1% cholesterol diet plus a non-hypotensive dose of perindopril (0.01 mg/kg per day); (iv) a normal diet; (v) a normal diet plus a hypotensive dose of perindopril (0.3 mg/kg per day); and (vi) a normal diet plus a non-hypotensive dose of perindopril (0.01 mg/kg per day). 4. After 6 weeks of treatment the animals were sacrificed. There were ameliorating effects of both hypotensive and non-hypotensive doses of perindopril on the development of plaques, as determined by the area of intima covered by Oil Red-O-staining plaque and light microscopy. 5. Cell culture studies indicated that perindopril has no effect on smooth muscle proliferation, but increases collagen and non-collagen synthesis by smooth muscle cells and decreases their binding of the atherogenic lipoprotein beta-very low density lipoprotein (beta-VLDL).(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanical pressure versus intrinsic effects of hypertension on large arteries in humans.

Brachial artery diameter and compliance were measured in 23 normotensive control subjects and 49 hypertensive patients. The results were compared in isobaric conditions by a modeling analysis extrapolating from the measured data a short segment of the pressure-diameter and pressure-compliance curves in the artery. A logarithmic diameter-pressure function was used as well as measurements of brachial artery blood pressure and lumen diameter (by pulsed Doppler), and of brachial-to-radial pulse wave velocity (by mechanography). The measured values of diameter and compliance in the hypertensive patients were 109% and 63%, respectively, of the control group values. By extrapolating the data via the model at the same pressure level in all subjects (the average level of mean blood pressure of the two groups), the isobaric values of diameter and compliance in the hypertensive patients were 107% and 81%, respectively, of the control group values. Overall, measured isobaric diameters and measured compliance correlated with systolic, diastolic, and mean blood pressure values (p less than 0.001), whereas isobaric compliance correlated only with systolic (p less than 0.05) and pulse (p less than 0.01) pressure values. Thus, the increased diameter and reduced compliance of the brachial artery observed in hypertensive humans cannot be attributed solely to the stretching effect of elevated blood pressure, but also to intrinsic alteration of the arterial walls. These could represent either adaptative structural or functional changes secondary to the chronic increase in arterial pressure, or primary abnormalities of the vessel wall.

Flow-dependent stimulation of sodium and cholesterol uptake and cell growth in cultured vascular smooth muscle.

A10 vascular smooth muscle cells were placed in a flow chamber and exposed to the circulation of foetal calf serum at different rates and pressures. Under unidirectional laminar flow, physiological flow rates and pressures had almost no effect on internal sodium content. Indeed, pressure values greater than 150 mmHg were required to observe modest increases in sodium content. Conversely, a short exposure to turbulent flow (3 min) induced a strong increase in cell sodium content. At flow rates found in large human arteries, the onset of such ionic change required pressure levels of 50-85 mmHg. The restoration of laminar flow allowed the elimination of the excess cell sodium content, with a half-life of 3-4 h. Opening of calcium channels by the turbulent flow was suggested by the following observations: (1) nitrendipine fully prevented sodium uptake, with an inhibitory concentration of 50% of approximately 2 x 10(-7) mol/l; and (2) exposure to turbulent flow increased cytosolic free calcium content by approximately 80%. In addition to sodium uptake, turbulent flow stimulated cell uptake of exogenous cholesterol. Although the restoration of laminar flow allowed the rapid elimination of approximately two-thirds of the excess in cell cholesterol (with a half-life of 30-60 min), one-third of the excess cholesterol remained in the cells for more than 24 h. Finally, cell replication was faster in cells exposed to turbulent flow than in control cells subjected to laminar flow. The results show that turbulent flow provokes membrane ion transport changes in vascular smooth muscle cells, which are associated with enhanced cholesterol uptake and cell hyperplasia. Therefore, the departure from unidirectional laminar flow may be a pathogenic factor in primary hypertension and/or atherosclerosis.

Cigarette smoking produces constriction of large coronary arteries in humans

Cigarette smoking produces constriction of large coronary arteries in humans

A new geometric procedure forIn vivo pulsed doppler evaluation of velocity distribution inside the diametrical section of large arteries in humans

A new geometric procedure determination of velocity profiles inside large human arteries, such as the brachial and femoral, has been developed. The procedure requires the use of two crystal element Doppler probes and a highly precise micromanipulator with three degrees of freedom. Precise positioning is needed to obtain the required high degree of parallelism between the vessel axis and the plane containing the two crystal elements. Once the appropriate degree of parallelism is achieved, a controlled translation of the probe, perpendicular to the ultrasonic beam plane, allows velocity waveforms to be recorded at sequential radial positions across the measured artery. Velocity profiles obtained with this geometric procedure depended on the type of artery investigated. The profiles measured with the geometric procedure were more symmetrical than those found using the electronic range-gated time system of reception. While the geometric and electronic methods were almost identical in determining the diameter values of the three arteries measured, the geometric procedure enabled greater accuracy for detailed analysis of velocity profiles in the peripheral large arteries in humans. Although the present methodology is not applicable in clinical practice due to prolonged data acquisition time (approximately 45 s) it is expected that future equipment improvements will reduce this time significantly.

A123 Lidocaine alters flow-mediated changes In large arteries in humans

A123 Lidocaine alters flow-mediated changes In large arteries in humans

Non-invasive evaluation of segmental pressure drop and resistance in large arteries in humans based on a Poiseuille model of intra-arterial velocity distribution

The aim of the study was to evaluate in hypertensive subjects the longitudinal pressure drop and segmental resistance in a large artery in relation to shearing forces of the circulating blood column at the arterial wall. Arterial diameter, blood velocity, and flow were measured in the brachial artery using pulsed Doppler apparatus. Blood viscosity was measured at 96 s-1 with a low shear viscometer. Segmental resistance per unit arterial length was calculated using the basic Poiseuille resistance expression from the ratio between blood viscosity and the fourth power of arterial diameter. Longitudinal pressure drop was deduced as the product between segmental resistance and blood flow. The Poiseuille model of velocity distribution also enabled wall shear rate and stress to be calculated from the ratio between blood velocity and arterial diameter and from the product between shear rate and blood viscosity respectively. 19 ambulatory male patients with mild to moderate hypertension and 11 normotensive male controls of similar age were studied. Compared to controls, hypertensive patients had higher arterial diameter (p less than 0.001) lower blood velocity (p less than 0.05), higher blood viscosity (p less than 0.01), lower segmental resistance and pressure drop (p less than 0.001, p less than 0.01) and lower shear rate and stress (p less than 0.01, p less than 0.05). A negative correlation existed in the overall normotensive and hypertensive population between pressure drop and mean blood pressure (r = -0.55, p less than 0.01). The hypertensive state is associated with a clear reduction in large artery segmental resistance and longitudinal pressure drop concomitantly with a decrease in shear conditions at the arterial wall. The mechanisms of reduced resistance and pressure drop are related to decreased wall shear and increased diameter of the artery, both of which reduce the frictional forces at the blood-arterial wall interface.

Large coronary arteries in humans are responsive to changing blood flow: An endothelium-dependent mechanism that fails in patients with atherosclerosis

Changes in blood flow can alter vasomotion of conduit arteries. This study examined vasomotor responses to incremental blood flow induced by papaverine in the epicardial arteries of 10 patients with angiographically normal coronary arteries (group 1) and in 14 patients with arterial irregularities (group 2) using quantitative angiography and Doppler ultrasound flow velocity measurements. An increase in coronary blood flow of 384.3 ± 32.8% (p < 0.001) in group 1 patients was associated with dilation of the proximal coronary artery segment and a 23.2 ± 4.6% increase in cross-sectional area (p < 0.001). In contrast, in group 2 patients a similar increase in coronary blood flow of 339.3 ± 18.7% (p < 0.001) was associated with mixed responses and a Modest net constriction in cross-sectional area of -7.4 ± 2.8% (p < 0.05). The dilation response to nitroglycerin was intact in group 1 (31.7 ± 4.2%, p < 0.001) and in group 2 (26.4 ± 3.2%, p < 0.001).In five patients from group 1 acetylcholine, an endothelium-dependent dilator, produced an increase in cross-sectional area of 20.7 ± 4.6% (p < 0.05) that paralleled the response to an increase in flow in the same segment (a 24.3 ± 6.1% increase in cross-sectional area, p < 0.05). Five group 21 patients demonstrated a vasoconstrictor response to acetylcholine (a − 22.8 ± 3.4% decrease in cross-sectional area, p < 0.05) together with an impaired dilation response to incremental flow (a − 6.4 ± 3.2% decrease in cross-sectional area). Thus, the normal flow-mediated dilation of coronary arteries is lost in atherosclerosis and this impairment may be due to endothelial cell vasodilator dysfunction.