Luminal morphology of small arterial vessels in the contracted spleen,studied by scanning electron microscopy of microcorrosion casts

Unique luminal configurations exhibited by small arterial vessels in contracted spleens of dog and cat were studied by means of vascular corrosion casts examined by scanning electron microscopy. Concertina-like pleating was seen in casts of trabecular arteries/arterioles, whereas within lymphatic nodules arteriolar casts lacked pleating and were smooth and uniformly cylindrical (as were all small arterial vessels in distended spleens). Morphological details of arterial vessels observed in histological sections indicated that pleating is not due to contraction of specially arranged vascular smooth muscle but to overall shortening of trabecular arterial vessels, caused by contraction of longitudinal smooth muscle in trabeculae. Another phenomenon observed in casts from contracted spleens was an almost complete "pinching-off" of many arteriolar lumens; histological evidence indicated that this is due to contraction of vascular smooth muscle, which selectively diverts flow away from certain regions of the organ. Also noted was a markedly convoluted, tortuous configuration of arterioles (penicilli) in the red pulp of contracted spleens.     

4-Aminopyridine antagonizes the acute relaxant action of metformin on adrenergic contraction in the ventral tail artery of the rat

The ability of metformin (MF) to acutely relax phenylephrine (PE)-induced contraction in the isolated rat tail artery is reported to be accompanied by repolarization of the arterial smooth muscle cell (SMC) membranes. These membranes contain potassium (K) channels which if opened could mediate such repolarization and resultant relaxation. We have shown that the acute relaxation of rat tail arterial tissue rings by graded levels of MF > or = 0.24 mmol/L is markedly antagonized by a high concentration of tetraethylammonium (TEA; 10 mmol/L) which nonselectively inhibits nearly all K channels. Thus, we tested effects of more selective inhibitors of K channels in the same tissue. We also tested MF for relaxation of contractions induced by high levels of extracellular K. To avoid confounding variables, we also conducted these tests in arterial rings in which endothelium and sympathetic nerve endings had been removed. In the absence of K channel inhibition, half-maximal PE-induced contractions were rapidly relaxed by all levels of MF with an EC50 of 1.7+/-0.2 mmol/L (n=8 rings). 1 mmol/L 4-aminopyridine (4AP) which only inhibits voltage-operated and ATP-sensitive K channels markedly antagonized this relaxation, shifting the EC50 for MF to 7.5+/-0.7 mmol/L (n=8; p < 0.05). TEA at 1 mmol/L (which only inhibits calcium-activated K channels), barium at 20 micromol/L (which only inhibits inward rectifier K channels) and glyburide at 5 micromol/L (which only inhibits ATP-sensitive K channels) did not alter this relaxation. Finally, MF failed to relax contractions produced by elevations of extracellular K to levels high enough to abolish the K gradient across arterial SMC membranes. Thus, acute relaxation of rat tail arterial smooth muscle by MF may be dependent on the transmembrane K gradient and mediated at least in part by specific activation of K efflux through 4AP-sensitive voltage-dependent K channels in arterial SMC membranes.     

Vascular smooth muscle and neurohypophyseal hormones.

Experimental studies relating to the direct peripheral vascular actions of neurohypophyseal hormones and their synthetic variants are reviewed. In addition, the available data on the comparative pharmacologic actions of these peptides on mammalian vascular smooth muscle are reviewed. Experiments relating to mechanisms by which neurohypophyseal peptides induce contraction of blood vessels are discussed. Neurohypophyseal peptide hormones appear to be able to contract and relax vascular smooth muscle, the exact type of response being dependent on species, vascular bed, and region within a vascular bed. Receptors that subserve both contraction and relaxation may exist on different blood vessels within a species, with a preponderance of receptors that subserve contraction being present in most blood vessels. Concentrations of vasopressin that can be considered physiologic (i.e., 10(-13) to 10(-11) M) are capable of evoking responses on a variety of microscopic as well as large blood vessels. Arginine-vasopressin appears to be, relatively, the most potent contractile substance on rat blood vessels investigated to date; angiotensin is not. Preservative-free oxytocin is a contractile agent on all mammalian arterial and arteriolar vessels so far investigated. A great deal of the controversy surrounding the exact vascular actions elicited by these peptide hormones can be attributed to many factors that were not controlled in older experiments. Moreover, rat pressor assays cannot be utilized to determine structure-activity relationship for neurohypophyseal peptides on vascular smooth muscles. Nuerohypophyseal peptide-induced contractions of vascular smooth muscles can be markedly affected by sex, sex hormones, alcohols, [Ca2+]0, [mg2+]0, oxygen deficit, and glucose-deprivation. Extracellular sodium and potassium ions appear to play relatively little role in vasopressin-induced contractions of rat arterial smooth muscle. The terminal amino group, phenolic hydroxyl, aromatic ring and basicity in positions 1, 2, 3, and 8, respectively, of the neurohypophyseal hormones are important for optimizing hormone-receptor affinity and intrinsic contractile activity on vascular smooth muscle. Basicity in position 8 of these peptide hormones is not an absolute requirement for contractile activation of these smooth muscles. Alterations in molecular structure can result in neurohypophyseal peptides with unique, and selective, microcirculatory effects that may be beneficial in the treatment of low-flow states.     

Telokin expression and the effect of hypoxia on its phosphorylation status in smooth muscle cells from small and large pulmonary arteries

Small pulmonary arteries (SPA), <500 microm diameter of the cat, constrict when exposed to hypoxia, whereas larger arteries (large pulmonary arteries; LPA), >800 microm diameter, show little or no response. It is unknown why different contractile responses occur within the same vascular bed, but activator or repressor proteins within the smooth muscle cell (SMC) can modify myosin phosphatase and myosin light chain kinase (MLCK), thereby influencing the phosphorylation state of myosin light chain (MLC) and ultimately, contraction. Telokin, a protein with a sequence identical to the COOH-terminal domain of MLCK, is expressed in smooth muscle where in its phosphorylated state it inhibits myosin phosphatase, binds to unphosphorylated myosin, and helps maintain smooth muscle relaxation. We measured telokin mRNA and telokin protein in smooth muscle from different diameter feline pulmonary arteries and sought to determine whether changes in the phosphorylation status of telokin and MLC occurred during hypoxia. In pulmonary arteries, telokin expression varied inversely with artery diameter, but cerebral arteries showed neither telokin protein nor telokin mRNA. Although telokin and MLC were distributed uniformly throughout the SPA muscle cell cytoplasm, they were not colocalized. During hypoxia, telokin dephosphorylated, and MLC became increasingly phosphorylated in SPA SMC, whereas in LPA SMC there was no change in either telokin or MLC phosphorylation. When LPA SMC were exposed to phenylephrine, MLC phosphorylation increased with no change in telokin phosphorylation. These results suggest that in SPA, phosphorylated telokin may help maintain relaxation under unstimulated conditions, whereas in LPA, telokin's function remains undetermined.     

Animal model for angiotensin II effects in the internal anal sphincter smooth muscle: mechanism of action

Effect of ANG II was investigated in in vitro smooth muscle strips and in isolated smooth muscle cells (SMC). Among different species, rat internal and sphincter (IAS) smooth muscle showed significant and reproducible contraction that remained unmodified by different neurohumoral inhibitors. The AT(1) antagonist losartan but not AT(2) antagonist PD-123319 antagonized ANG II-induced contraction of the IAS smooth muscle and SMC. ANG II-induced contraction of rat IAS smooth muscle and SMC was attenuated by tyrosine kinase inhibitors genistein and tyrphostin, protein kinase C (PKC) inhibitor H-7, Ca(2+) channel blocker nicardipine, Rho kinase inhibitor Y-27632 or p(44/42) mitogen-activating protein kinase (MAPK(44/42)) inhibitor PD-98059. Combinations of nicardipine and H-7, Y-27632, and PD-98059 caused further attenuation of the ANG II effects. Western blot analyses revealed the presence of both AT(1) and AT(2) receptors. We conclude that ANG II causes contraction of rat IAS smooth muscle by the activation of AT(1) receptors at the SMC and involves multiple intracellular pathways, influx of Ca(2+), and activation of PKC, Rho kinase, and MAPK(44/42).     

A logistic-type curve fits pressure-diameter relationship for relaxed and contracted dog renal arteries

In order to describe a possible effect of smooth muscle cell (SMC) activation on arterial wall distensibility, the present study derived a mathematical equation applicable to relaxed and contracted arterial walls. Pressure(P)-diameter(D) relationship of dog renal arteries was investigated in vitro under a cyclic loading and unloading process in the pressure range of 5-180 mmHg. Smooth muscle cells were activated by 10(-5)M norepinephrine. On the basis of the P-D curves obtained with fully contracted arteries, the vessel wall compliance dD/dP was assumed to be given by a second order polynomial of D, (formula; see text) The equation, including three parameters, Dmin, Dmax, and E, is integrated to yield the solution similar to the logistic curve as follows (formula; see text) where M(O) = (Dmax - D(O]/(D(O) - Dmin), and D(O) is the diameter at the point P = O. The constant, E, has the same dimension as the modulus of elasticity. The calculated P-D relationships coincided well with the experimental data for contracted and relaxed arteries. The most significant change due to wall contraction took place in the magnitude of M. This result, therefore, suggests that the parameter M is a good index of the degree of SMC contraction.     

Increased gelsolin expression and retarded collagen lattice contraction with smooth muscle cells from Crohn's diseased intestine

Intestinal smooth muscle cells (SMC) produce the fibrotic tissue, strictures, that characterize Crohn's disease. These SMC change their phenotype from a contractile muscle form to an inflammation-responsive form that migrates and synthesizes a collagen matrix. It is postulated that the inflammatory responsive SMC form associates differently with its surrounding collagen matrix compared to the normal SMC form. SMC derived from Crohn's diseased and uninvolved bowel were sustained in cell culture. Cultured SMC incorporated in collagen lattices have the capacity to reduce the size of that lattice, referred to as lattice contraction. At day 2, Crohn's SMC-populated collagen lattices were reduced to 21% of their initial area, while non-Crohn's SMC collagen lattices were reduced to 8%. Crohn's SMC demonstrate retarded lattice contraction compared to non-Crohn's SMC. When grown in monolayer culture, Crohn's-derived SMC cover 30% more area than non-Crohn's SMC. By Western blot analysis Crohn's SMC express more gelsolin, an actin-binding protein found elevated in cells exhibiting increased cell motility. Was the increased expression of gelsolin related to retarded collagen lattice contraction? Intracellular levels of gelsolin were elevated by the electroporation of plasma gelsolin protein into suspended non-Crohn's SMC. When incorporated in collagen lattices, gelsolin loaded cells showed retarded lattice contraction compared to SMC loaded with albumin. Crohn's SMC show increased expression of gelsolin, which may be associated with a diminished capacity to reorganize collagen fiber bundles. It is suggested that increased concentrations of gelsolin in Crohn's SMC is consistent with enhanced cell migration as a consequence of the inflammatory state of Crohn's diseased intestine.     

Differences in the mechanism of collagen lattice contraction by myofibroblasts and smooth muscle cells

Both rat derived vascular smooth muscle cells (SMC) and human myofibroblasts contain α smooth muscle actin (SMA), but they utilize different mechanisms to contract populated collagen lattices (PCLs). The difference is in how the cells generate the force that contracts the lattices. Human dermal fibroblasts transform into myofibroblasts, expressing α‐SMA within stress fibers, when cultured in lattices that remain attached to the surface of a tissue culture dish. When attached lattices are populated with rat derived vascular SMC, the cells retain their vascular SMC phenotype. Comparing the contraction of attached PCLs when they are released from the culture dish on day 4 shows that lattices populated with rat vascular SMC contract less than those populated with human myofibroblast. PCL contraction was evaluated in the presence of vanadate and genistein, which modify protein tyrosine phosphorylation, and ML‐7 and Y‐27632, which modify myosin ATPase activity. Genistein and ML‐7 had no affect upon either myofibroblast or vascular SMC‐PCL contraction, demonstrating that neither protein tyrosine kinase nor myosin light chain kinase was involved. Vanadate inhibited myofibroblast‐PCL contraction, consistent with a role for protein tyrosine phosphatase activity with myofibroblast‐generated forces. Y‐27632 inhibited both SMC and myofibroblast PCL contraction, consistent with a central role of myosin light chain phosphatase. J. Cell. Biochem. 111: 362–369, 2010. © 2010 Wiley‐Liss, Inc.     

Effects of arterial wall stress on vasomotion

Smooth muscle and endothelial cells in the arterial wall are exposed to mechanical stress. Indeed blood flow induces intraluminal pressure variations and shear stress. An increase in pressure may induce a vessel contraction, a phenomenon known as the myogenic response. Many muscular vessels present vasomotion, i.e., rhythmic diameter oscillations caused by synchronous cytosolic calcium oscillations of the smooth muscle cells. Vasomotion has been shown to be modulated by pressure changes. To get a better understanding of the effect of stress and in particular pressure on vasomotion, we propose a model of a blood vessel describing the calcium dynamics in a coupled population of smooth muscle cells and endothelial cells and the consequent vessel diameter variations. We show that a rise in pressure increases the calcium concentration. This may either induce or abolish vasomotion, or increase its frequency depending on the initial conditions. In our model the myogenic response is less pronounced for large arteries than for small arteries and occurs at higher values of pressure if the wall thickness is increased. Our results are in agreement with experimental observations concerning a broad range of vessels.     

Contraction of human colonic circular smooth muscle cells is inhibited by the calcium channel blocker pinaverium bromide

The effects of L-type calcium channel blockers (CCBs) selective for the gastrointestinal tract (pinaverium) or non-selective (nicardipine and diltiazem), were investigated on CCK-, CCh- or KCl-induced contraction of smooth muscle cells (SMC) isolated from the circular muscle layer of normal or of inflamed human colons. In the normal tissue colon, whatever the contractile agent used, CCK-8 (1nM), CCh (1nM) or KCl (20mM), a micromolar concentration of pinaverium significantly inhibited contraction (88.36%, 93.10%, 93.92% inhibition respectively); this effect was concentration-dependent for CCh (IC50 = 0.73 +/- 0.08nM) and for CCK (IC50 = 0.92 +/- 0.12nM). In parallel, both nicardipine and diltiazem inhibit significantly contraction of isolated SMC. In inflamed colons, pinaverium (1 microM) display a significant higher efficacy than diltiazem or nicardipine to reduce cell contraction induced by CCK-8 or by KCl. In addition, RT-PCR experiments were performed to evidence tissue specificity of the L-type calcium channel. They revealed the expression of the messenger of the a-1 subunit L-type calcium channel (binding site of such CCBs), consistent with the expression of the rbC-2 splice variant of the alpha1-C gene.In conclusion: (i) the inhibition by calcium channel blockers of agonist-induced contractile activity suggest a modulation of SMC contraction upon extracellular calcium via 'L-type' voltage-dependent calcium channel; (ii) this study provides a rationale for the clinical use of pinaverium in colonic motor disoders affecting the contractility of SMC, since it appeared to decrease the contraction even in pathological situation; and (iii) RT-PCR experiments confirms the presence in human colon SMC of the alpha-1 subunit mRNA of calcium channel.     

Regional differences in signalling transduction pathways among smooth muscle cells from rabbit colon

Smooth muscle cells (SMC) from the circular muscle layer of rabbit colon, taken from the proximal and distal regions that are known to have different physiological and motor activities, were used to highlight distinct regional intrinsic myogenic properties and to investigate the correlations between receptor and signalling transduction pathways. Contractile agonists were shown to be more potent on proximal than on distal SMC in inducing contraction and intracellular Ca(2+) increase. Concentration-response curves of agonists-induced Ca(2+) increase were constantly shifted to the right, though remaining parallel, with respect to contraction curves, independently of the region analysed. Using agents activating different steps of cAMP-or cGMP-mediated intracellular cascades, main regional differences were revealed as far as relaxation was concerned. Relaxation of proximal SMC was found to be essentially cGMP mediated, while that of distal SMC was cAMP mediated. In conclusion, the motor patterns of the two regions appear to be influenced by distinct regional biochemical characteristics that are intrinsic to colonic SMC.     

Age characteristics of the effect of insulin on smooth muscle cells of the femoral artery

A study was made of the effects of insulin on smooth muscle cells (SMC) of the femoral artery of rats aged 6-8 and 24-26 months. Insulin hyperpolarized the SMC membrane and diminished the tone of smooth muscles of the vessels. These effects were dependent on the hormone concentration and perfusate temperature. In old animals, the sensitivity of smooth muscles of the vessels to insulin and the response to higher concentrations were reduced. It is believed that the changes described may play a definite role in the mechanisms by which the vascular tone is controlled.     

A mechanism for arteriolar remodeling based on maintenance of smooth muscle cell activation

Structural adaptation in arterioles is part of normal vascular physiology but is also seen in disease states such as hypertension. Smooth muscle cell (SMC) activation has been shown to be central to microvascular remodeling. We hypothesize that, in a remodeling process driven by SMC activation, stress sensitivity of the vascular wall is a key element in the process of achieving a stable vascular structure. We address whether the adaptive changes in arterioles under different conditions can arise through a common mechanism: remodeling in a stress-sensitive wall driven by a shift in SMC activation. We present a simple dynamic model and show that structural remodeling of the vessel radius by rearrangement of the wall material around a lumen of a different diameter and driven by differences in SMC activation can lead to vascular structures similar to those observed experimentally under various conditions. The change in structure simultaneously leads to uniform levels of circumferential wall stress and wall strain, despite differences in transmural pressure. A simulated vasoconstriction caused by increased SMC activation leads to inward remodeling, whereas outward remodeling follows relaxation of the vascular wall. The results are independent of the specific myogenic properties of the vessel. The simulated results are robust in the face of parameter changes and, hence, may be generalized to vessels from different vascular beds.     

Differentiation of the smooth muscle cell phenotypes during embryonic development of coronary vessels in the rat

Smooth muscle cell (SMC) maturation during embryonic development of coronary arteries and veins was studied in rats using different markers of the contractile phenotypes. The spatio-temporal pattern of distribution of these markers compared with the developing tunica media was examined. Alpha-smooth muscle actin (alpha-SMA) was the first marker of the SMC in the tunica media of coronary arteries found in ED16 hearts, followed by smooth muscle myosin heavy chain isoform which occurred on ED17. Subsequently 1E12 antigen was expressed in coronary artery wall in ED18 hearts, and finally smoothelin. The markers occur within the proximal part of the coronary arteries and deploy toward the apex. They are also found within the great vessels. None of the markers except for the alpha-SMA were found in coronary veins during embryonic life. We conclude that the SMC population of the developing tunica media of coronary vessels differentiates by the acquisition of particular markers and this process lasts till the end of the prenatal and early postnatal life.     

Effects of ischemia and myogenic activity on active and passive mechanical properties of rat cerebral arteries

Passive (papaverine induced) and active (spontaneous pressure induced) biomechanical properties of ischemic and nonischemic rat middle cerebral arteries (MCAs) were studied under pressurized conditions in vitro. Ischemic (1 h of occlusion), contralateral, and sham-operated control MCAs were isolated from male Wistar rats (n = 22) and pressurized using an arteriograph system that allowed control of transmural pressure (TMP) and measurement of lumen diameter and wall thickness. Three mechanical stiffness parameters were computed: overall passive stiffness (beta), pressure-dependent modulus changes (E(inc,p)), and smooth muscle cell (SMC) activity-dependent changes (E(inc,a)). The beta-value for ischemic vessels was increased compared with sham vessels (13.9 +/- 1.7 vs. 9.1 +/- 1.4, P < 0.05), indicating possible short-term remodeling due to ischemia. E(inc,p) increased with pressure in the passive vessels (P < 0.05) but remained relatively constant in the active vessels for all vessel types, indicating that pressure-induced SMC contractile activity (i.e., myogenic reactivity) in cerebral arteries leads to the maintenance of a constant elastic modulus within the autoregulatory pressure range. E(inc,a) increased with pressure for all conditions, signifying that changes in stiffness are influenced by SMC activity and vascular tone.     

Recruitment of smooth muscle cells and arterial vasomotion

Investigating the recruitment and synchronization of smooth muscle cells (SMCs) is the key to understanding the physical mechanisms leading to contraction and spontaneous diameter oscillations of arteries, called vasomotion. We improved a method that allows the correlation of calcium oscillations (flashing) of individual SMCs with mean calcium variations and arterial contraction using confocal microscopy. Endothelium-stripped rat mesenteric arteries were cut open, loaded with dual calcium fluorescence probes, and stimulated by increasing concentrations of the vasoconstrictors phenylephrine (PE) and KCl. We found that the number and synchronization of flashing cells depends on vasoconstrictor concentration. At low vasoconstrictor concentration, few cells flash asynchronously and no local contraction is detected. At medium concentration, recruitment of cells is complete and synchronous, leading to strip contraction after KCl stimulation and to vasomotion after PE stimulation. High concentration of PE leads to synchronous calcium oscillations and fully contracted vessels, whereas high concentration of KCl leads to a sustained nonoscillating increase of calcium and to fully contracted vessels. We conclude that the number of simultaneously recruited cells is an important factor in controlling rat mesenteric artery contraction and vasomotion.     

Mechanics of caudal artery relaxation in control and hypertensive rats

Alterations of smooth muscle function can just as easily stem from mechanical alterations in its ability to relax as from alteration in contraction. Since a failure of arterial smooth muscle to relax may contribute to the development of hypertension, we felt it necessary to study the relaxation process in greater depth. The effect of load on the time course of relaxation of rat caudal artery smooth muscle was analyzed either by comparing afterloaded contractions against various loads or by imposing abrupt alterations in load. Unlike mammalian striated muscles in which relaxation was reported sensitive to loading conditions, relaxation in the smooth muscle of the rat caudal artery (n = 17) was found to be largely independent of loading conditions. This type of relaxation has been termed "inactivation-dependent" relaxation; it is typical of muscle tissue in which the calcium sequestering apparatus is poorly developed. Our results suggest that calcium resequestration, or some biochemical process downstream to it, is the rate-limiting step during relaxation in arterial smooth muscle and that this is not qualitatively different for hypertensive arterial smooth muscle. These analytic techniques were used in the study of relaxation of hypertensive vessels. Quantitative analysis of the relaxation curves showed that both isometric and isotonic relaxation time was prolonged in hypertensive arterial smooth muscle. Prolonged isotonic relaxation indicates that hypertensive arteries remain narrowed for prolonged periods compared with normotensive vessels. Such narrowed vessels may be a factor in the increased total peripheral resistance seen in genetic hypertension.     

The Calcitonin Gene-Related Peptide Activates Both cAMP and NO Pathways to Induce Relaxation of Circular Smooth Muscle Cells of Guinea-Pig Ileum

Rekik, M., M. Delvaux, J. Frexinos, and L. Bueno. Calcitonin gene-related peptide activates both cAMP and NO pathways to induce relaxation of circular smooth muscle cells of guinea-pig ileum. Peptides 18(10) 1517–1522, 1997.—The direct effects and the intracellular pathways of rCGRP were investigated on smooth muscle cells (SMC) isolated by enzymatic digestion from the circular and longitudinal layers of guinea-pig ileum. In circular SMC, rCGRP inhibited CCK8-induced contraction in a concentration-dependent manner (Cmax = 100 μM and EC₅₀ = 0.7 ± 0.4 nM). Preincubation of SMC with 1 μM Rp-cAMPs, a cAMP antagonist, abolished the relaxing effect of rCGRP; moreover, preincubation of SMC with 100 μM L-NAME, an inhibitor of NOS, inhibited the relaxing effect of rCGRP. hCGRP(8-37), a selective antagonist of rCGRP receptors, inhibited the rCGRP-induced relaxation in a concentration dependent manner whereas the vasoactive intestinal polypeptide (VIP) antagonist had no significant effect. In longitudinal SMC, rCGRP-induced relaxation was abolished by Rp-cAMPs, whereas L-NAME had no effect. In conclusion, rCGRP triggers different intracellular pathways to induce relaxation of circular or longitudinal intestinal SMC; cAMP is involved in cells from both layers while nitric oxide (NO) is involved only in relaxation of circular SMC.     

Innervation of the umbilical vessels

Summary Umbilical vessels of guinea-pig fetuses were studied shortly before birth. In all umbilical cords investigated an innervation of the umbilical vessels is lacking. The intrafetal parts of the umbilical vessels on the other hand are richly innervated. A marked difference in the amount of nerve fibres and the pattern of innervation is found between artery and vein. The artery is supplied by a dense nerve plexus which spins around the media and which originates from nerve bundles within the outer adventitial layers. The comparatively scanty innervation of the vein exhibits a more coarsely meshed net pattern. The nerve bundles in the vein exhibit a close affinity to the vasa vasorum.Number and type of the close contacts between the muscle cells are different in the various sections of the umbilical vessels. Similar to the distribution of nerves they are almost absent in the vessels of the umbilical cord, numerously, however, in the intrafetal parts. Contrary to the innervation, the close contacts in the vein are developed more numerously and more broadly than in the corresponding artery.