Decreasing Vessel Size Research Articles

Vessel plasticity of European beech in response to thinning and aspect.

The importance of European beech (Fagus sylvatica L.) for the Central European forest and wood sector demands profound research to examine the adaptive capacity of beech forests to changing environmental conditions. Quantitative wood anatomy is a valuable tool for studying the relation between structural and functional traits of trees, but due to the laborious methodology not many studies have thus far been performed on the conductive tissue of broadleaf tree species with diffuse-porous wood structure. The aim of our research was to test the effects of aspect and thinning on vessel anatomical features of European beech (vessel density, vessel size, total vessel area, vessel groups and hydraulic conductivity). Our analysis of increment cores of trees sampled from a long-term experimental research area on the Swabian Alb showed that (i) the variations in different vessel traits were mainly controlled by tree-ring width. Additionally, we could observe that (ii) thinning contributed to a safer water transport by decreasing vessel size and that (iii) the aspect modified these responses. Our results provide new insights into the plastic response of European beech wood anatomy to warmer climatic conditions and demonstrated that thinning of the forest stands modified the water-conducting system to become more resistant against hydraulic failure.

Lysyl oxidase family activity promotes resistance of pancreatic ductal adenocarcinoma to chemotherapy by limiting the intratumoral anticancer drug distribution.

Solid tumors often display chemotherapy resistance. Pancreatic ductal adenocarcinoma (PDAC) is the archetype of resistant tumors as current chemotherapies are inefficient. The tumor stroma and extracellular matrix (ECM) are key contributors to PDAC aggressiveness and to limiting the efficacy of chemotherapy. Lysyl oxidase (LOX) family members mediate collagen cross-linking and thus promote ECM stiffening. Our data demonstrate increased LOX, LOXL1, and LOXL2 expression in PDAC, and that the level of fibrillar collagen, which is directly dependent of LOX family activity, is an independent predictive biomarker of adjuvant “Gemcitabine-based chemotherapy” benefit. Experimentally in mice, increased LOX family activity through LOXL2 promotes chemoresistance. This effect of LOX family activity seems to be due to decreased gemcitabine intra-tumoral diffusion. This observation might be explained by increased fibrillar collagen and decreased vessel size observed in tumors with increased LOX family activity. In conclusion, our data support that LOX family activity is both a novel target to improve chemotherapy as well as a novel biomarker to predict gemcitabine benefit in PDAC. Beyond the PDAC, it is possible that targeting LOX family activity might improve efficacy of chemotherapies against different kinds of solid tumors.

Microbubble oscillating in a microvessel filled with viscous fluid: A finite element modeling study

Understanding the dynamics of coated-microbubble oscillating in an elastic microvessel is important for effective and safe applications of ultrasound contrast agents (UCAs) in imaging and therapy. Numerical simulations are performed based on a two-dimensional (2D) asymmetric finite element model to investigate the influences of both acoustic driving parameters (e.g., pressure and frequency) and material properties (vessel size, microbubble shell visco-elastic parameters and fluid viscosity) on the dynamic interactions in the bubble–blood–vessel system. The results show that, the constrained effect of the blood vessel along the radial direction will induce the asymmetric bubble oscillation and vessel deformation, as well as shifting the bubble resonance frequency toward the higher frequency range. For a bubble (1.5-μm radius) activated by 1-MHz ultrasound pulses in a microvessel with a radius varying between 2 and 6.5μm, up to 26.95kPa shear stress could be generated on the vessel wall at a driving pressure of 0.2MPa, which should be high enough to damage the vascular endothelial cells. The asymmetrical oscillation ratio of the bubble can be aggravated from 0.12% to 79.94% with the increasing acoustic driving pressure and blood viscosity, or the decreasing vessel size and microbubble shell visco-elastic properties. The maximum compression velocity on the bubble shell will be enhanced from 0.19 to 22.79m/s by the increasing vessel size and acoustic pressure, or the decreasing microbubble shell visco-elasticity and blood viscosity. As the results, the peak values of microstreaming-induced shear stress on the vessel wall increases from 0.003 to 26.95kPa and the deformation degree of vessel is raised from 1.01 to 1.49, due to the enhanced acoustic amplitude, or the decreasing vessel size, blood viscosity and microbubble shell visco-elasticity. Moreover, it also suggests that, among above impact parameters, microbubble resonance frequency and UCA shell elasticity might play more dominant roles in dynamic interactions of the bubble–blood–vessel system.

Coronary vascular regulation, remodelling, and collateralization: mechanisms and clinical implications on behalf of the working group on coronary pathophysiology and microcirculation.

Histological specimen and textbook schematics evoke static pictures of vascular networks. However, the concept of a static system is grossly misleading as vessels and their arrangement into networks exhibit a high degree of adaptation in vessel tone and vessel wall structure.1–3 These adaptive responses include the fast adjustment of vessel diameter by changes in smooth muscle tone, the slower changes of structural vessel diameter, the addition or removal of vessels by angiogenesis (sprouting/splitting), or vascular pruning ( Figure 1 ). It is relevant to distinguish physiological adaptation, maintaining an adequate state of perfusion as well as perfusion reserve, from mal-adaptation, which may occur in the context of pathological conditions, such as a persistent increase in blood pressure. There are also differences between regulatory mechanisms in larger vessels (e.g. remodelling at the site of epicardial stenosis) and those in the microcirculation. Even within the microcirculation vascular control mechanisms are highly dependent on vessel size and type and the extent of changes in vasomotor tone and structure seem to increase with decreasing vessel size.4,5 Adaptive processes in the microcirculation are increasingly emerging as being crucial for maintenance of physiological function and for the development of relevant pathological conditions. This part of the coronary circulation, exhibiting that functional and structural plasticity requires more attention in both basic and clinical science as the basis to develop improved diagnostic and therapeutic approaches. Consequently, the present review will focus on adaptive events occurring in the coronary microcirculation which is beyond the domain of catheter investigation and intravascular imaging. Figure 1 Dynamics of vascular adaptation at various time scale (angioadaptation).57 While tone provides a rapid mechanism to adjust perfusion …

Noninvasive Measurements and Analysis of Blood Velocity Profiles in Human Retinal Vessels

To quantitatively model the changes in blood velocity profiles for different cardiac phases in human retinal vessels. An adaptive optics scanning laser ophthalmoscope (AOSLO) was used to measure blood velocity profiles in three healthy subjects. Blood velocity was measured by tracking erythrocytes moving across a scanning line. From the radial position of the cells within the lumen, the blood velocity profile was computed. The cardiac pulsatility was recorded with a cardiac signal monitor. The shape of the blood velocity profile in retinal arteries changed systematically during the cardiac cycle, with the flattest profile occurring during the diastolic phase. The measured blood velocity profiles were typically flatter than the commonly assumed parabolic shape. The flatness increased with decreasing vessel size. For the large veins (>80 μm), the ratio of the centerline velocity to the cross-sectional average velocity was between 1.50 and 1.65. This ratio decreased to 1.36 in the smallest vein studied (32 μm). Velocity profiles downstream from a venous confluence showed two peaks at 120 μm from the confluence, but a single velocity peak 500 μm downstream from the confluence. The cardiac cycle influences the blood flow velocity profiles systematically in retinal arteries but not in veins. Parabolic flow was not found in even the largest vessels studied, and deviations from parabolic flow increased in smaller vessels. The measurements are sensitive enough to measure the dual-humped blood velocity profile at a vein confluence.

Matrix Metalloproteinases Contribute Distinct Roles in Neuroendocrine Prostate Carcinogenesis, Metastasis, and Angiogenesis Progression

Prostate cancer is the leading form of cancer in men. Prostate tumors often contain neuroendocrine differentiation, which correlates with androgen-independent progression and poor prognosis. Matrix metalloproteinases (MMP), a family of enzymes that remodel the microenvironment, are associated with tumorigenesis and metastasis. To evaluate MMPs during metastatic prostatic neuroendocrine cancer development, we used transgenic mice expressing SV40 large T antigen in their prostatic neuroendocrine cells, under the control of transcriptional regulatory elements from the mouse cryptdin-2 gene (CR2-TAg). These mice have a stereotypical pattern of tumorigenesis and metastasis. MMP-2, MMP-7, and MMP-9 activities increased concurrently with the transition to invasive metastatic carcinoma, but they were expressed in different prostatic cell types: stromal, luminal epithelium, and macrophages, respectively. CR2-TAg mice treated with AG3340/Prinomastat, an MMP inhibitor that blocks activity of MMP-2, MMP-9, MMP-13, and MMP-14, had reduced tumor burden. CR2-TAg animals were crossed to mice homozygous for null alleles of MMP-2, MMP-7, or MMP-9 genes. At 24 weeks CR2-TAg; MMP-2(-/-) mice showed reduced tumor burden, prolonged survival, decreased lung metastasis, and decreased blood vessel density, whereas deficiencies in MMP-7 or MMP-9 did not influence tumor growth or survival. Mice deficient for MMP-7 had reduced endothelial area coverage and decreased vessel size, and mice lacking MMP-9 had increased numbers of invasive foci and increased perivascular invasion, as well as decreased tumor blood vessel size. Together, these results suggest distinct contributions by MMPs to the progression of aggressive prostate tumor and to helping tumors cleverly find alternative routes to malignant progression.

The Natural Frequency of Nonlinear Oscillation of Ultrasound Contrast Agents in Microvessels

Ultrasound contrast agents (UCAs) are under intensive investigation for their applications in physiological and molecular imaging and drug delivery. Prediction of the natural frequency of the oscillation of UCAs in microvessels has drawn increasing attention. To our knowledge, the existing models to predict the natural frequency of oscillation of UCAs in microvessels all apply the linear approximation and treat the blood vessel wall as a rigid boundary. In the potential applications of ultrasound imaging drug and gene delivery, the compliance of small vessels may play an important role in the bubble’s oscillation. The goal of this work is to provide a lumped-parameter model to study the natural frequency of nonlinear oscillation of UCAs in microvessels. Three types of the blood vessel conditions have been considered: i.e., rigid vessels, normal compliable vessels and vessels with increasing stiffness that could correspond to tumor vasculature. The corresponding bubble oscillation frequencies in vessels with a radius less than 100 μm are examined in detail. When a bubble with a radius of 4 μm is confined in a compliable vessel (inner radius 5 μm and length 100 μm), the natural frequency of bubble oscillation increases by a factor of 1.7 compared with a bubble in an unbounded field. The natural frequency of oscillation of a bubble in a compliable vessel increases with decreasing vessel size while decreasing with increasing values of vessel rigidity. This model suggests that contrast agent size, blood vessel size distribution and the type of vasculature should comprehensively be considered for choosing the transmitted frequency in ultrasound contrast imaging and drug delivery. (E-mail: spqin@ucdavis.edu)

The natural frequency of nonlinear oscillation of ultrasound contrast agents in microvessels

Prediction of natural frequency of oscillation of ultrasound contrast agents (UCAs) in microvessels plays an important role in UCA imaging and drug delivery. Here, the natural frequency of a microbubble in microvessels was studied in detail. Three models for blood vessel compliance have been considered, i.e., a rigid vessel, normal compliant vessel, and a stiff vessel which may correspond to the tumor-developing vasculature. Numerical results demonstrate that the natural frequency of a bubble in a rigid vessel is substantially decreased as compared to that in an unbounded field. However, within a compliant vessel, the natural frequency of bubble oscillation increases with decreasing vessel size. When a bubble with a radius of 4 m is confined in a compliant vessel (inner radius 5 m and length 100 m), the natural frequency of bubble oscillation increases by a factor of 1.7 as compared with that in an unbounded field. The natural frequency of bubble oscillation in a compliant vessel decreases with increasing values of vessel rigidity. This model suggests that contrast agent size, blood vessel size distribution, and the type of vasculature should be comprehensively considered for choosing the transmitted frequency in UCA imaging and drug delivery. [Work supported by NIH CA 103828.]

EDHF and Gap Junctions: Important Regulators of Vascular Tone Within the Microcirculation

Arterioles within the microcirculation control organ blood flow and represent the main peripheral resistance within the circulation. However, larger vessels with a diameter of more than 150 microm are mostly used to study vascular behavior. Although arterioles have features in common with these conducting vessels, they exhibit distinct properties and the contribution of different pathways to constriction or relaxation varies with vessel size. This is especially the case for endothelium-dependent relaxations, which occur in response to mechanical stimuli (e.g. blood flow) and agonists. Autacoids released from the endothelium include nitric oxide, prostaglandins and an endothelium-derived hyperpolarizing factor (EDHF). Whereas nitric oxide is dominant in larger vessels, the importance of EDHF increases with decreasing vessel size. Its chemical nature is still a matter of debate and different substances have been identified to act as an EDHF in different vascular beds, e.g. epoxyeicosanoids, potassium ions, anandamide, hydrogen peroxide or C-type natriuretic peptide. Despite this heterogeneity of proposed factors it is unclear if such a factor indeed exists in all vessels since the hyperpolarization of vascular smooth muscle has been proposed to be induced by simple current transfer from the adjacent endothelium. For this to occur the cells need to be electrically coupled and this requirement is fulfilled by gap junctions which are composed of connexins forming intercellular channels. Aside from myoendothelial coupling gap junctions also interconnect endothelial cells thus creating a functional unit, which efficiently synchronizes cellular behavior within the arteriolar tree of the microcirculation.

Old Bone Marrow Cells Inhibit Skin Wound Vascularization

Local injection of hematopoietic stem cell-enriched cells, including mouse lin- cells, accelerates vascularization in animal injury models, apparently by release of angiogenic factors. Locally injected lin- cells from nondiabetic mice dramatically improve, but those from obese diabetic mice inhibit vascular growth in obese diabetic mouse skin wounds. Because of similarities between diabetes and aging and because autologous bone marrow-derived cells are currently being tested in clinical trials involving older patients, we investigated the effects of old lin- cells on skin wound vascularization in nondiabetic and obese diabetic mice. Treatment with old lin- bone marrow cells resulted in decreased vessel size and numerical density, leading to profoundly reduced vascular volume density in wounds of non-diabetic and diabetic mice. Our data suggest that bone marrow-derived cells may be poor candidates for therapeutic use in older patients and could actually harm them.

Substantiation of a lower estimate for the bunker inventory: Comment on “Updated emissions from ocean shipping” by James J. Corbett and Horst W. Koehler

Substantiation of a lower estimate for the bunker inventory: Comment on “Updated emissions from ocean shipping” by James J. Corbett and Horst W. Koehler

Angiographic analysis of the angioplasty versus rotational atherectomy for the treatment of diffuse in-stent restenosis trial (ARTIST)

Patients with diffuse in-stent restenoses (ISRs) are at high risk for recurrent restenosis after percutaneous transluminal balloon angioplasty (PTCA). Percutaneous transluminal rotational ablation (PTCR) has proved effective in removing neointimal burden in ISRs. This study compares the acute and long-term results of PTCA and PTCR for the treatment of diffuse ISR in a randomized, multicenter investigation. The primary end point was the comparison of the minimum luminal diameter (MLD) between both groups at 6-month follow-up. Patients with symptomatic, diffuse, or high-grade ISRs were included; 146 patients were randomized to PTCA and 152 patients to PTCR. Diameter stenosis was reduced from 80 ± 12% to 29 ± 10% and from 80 ± 11% to 28 ± 12%, respectively, and MLD increased from 0.55 ± 0.3 to 1.9 ± 0.3 mm in the PTCA group and from 0.54 ± 0.3 mm to 1.9 ± 0.4 mm in the PTCR group. Spasm in the treated vessel and an intermittent slow flow phenomenon occurred more often after rotational ablation (17.7% vs 8.6%, p = 0.001; 5.3% vs 0%, p = 0.007). Minimum stenosis diameter at 6-month follow-up was smaller in the PTCR group than in the PTCA group (1.0 ± 0.6 vs 1.2 ± 0.6 mm, p = 0.008) and the restenosis rate was higher (64.9% vs 51.2%, p = 0.027). Procedural factors did not influence long-term outcome. In the PTCR group, the restenosis rate increased with decreasing vessel size, whereas this was not seen in the PTCA group. The lesion length and the baseline diameter stenosis were found to be predictive of restenosis with both treatment strategies; however, a residual diameter stenosis of <30% predicted absence of a restenosis only in the PTCR group. Thus, PTCA and PTCR of diffuse ISRs yield comparable acute angiographic results. The recurrence of a restenosis is higher after PTCR than after PTCA.

Invited Commentary

Invited Commentary

Flow Resistance and Drag Forces Due to Multiple Adherent Leukocytes in Postcapillary Vessels

Computational fluid dynamics was used to model flow past multiple adherent leukocytes in postcapillary size vessels. A finite-element package was used to solve the Navier-Stokes equations for low Reynolds number flow of a Newtonian fluid past spheres adhering to the wall of a cylindrical vessel. We determined the effects of sphere number, relative geometry, and spacing on the flow resistance in the vessel and the fluid flow drag force acting to sweep the sphere off the vessel wall. The computations show that when adherent leukocytes are aligned on the same side of the vessel, the drag force on each of the interacting leukocytes is less than the drag force on an isolated adherent leukocyte and can decrease by up to 50%. The magnitude of the reduction depends on the ratio of leukocyte to blood vessel diameter and distance between adherent leukocytes. However, there is an increase in the drag force when leukocytes adhere to opposite sides of the vessel wall. The increase in resistance generated by adherent leukocytes in vessels of various sizes is calculated from the computational results. The resistance increases with decreasing vessel size and is most pronounced when leukocytes adhere to opposite sides of the vessel.

Review of alterations in endothelial nitric oxide production in diabetes: protective role of arginine on endothelial dysfunction.

Nitric oxide release from the endothelium plays an important role in regulation of vascular tone, inhibition of both platelet and leukocyte aggregation and adhesion, and inhibition of cell proliferation. These properties suggest that the level of NO production by the endothelium may play a pivotal role in the regulation of vascular disease. Analysis using mass spectrometry has revealed that NO is produced by NOS from the terminal guanidino nitrogen of the precursor amino acid L-arginine. Thus, utilization of L-arginine and conversion to NO may establish a regulatory site in the development of endothelial dysfunction. Endothelial dysfunction is characterized by defective endothelium-dependent relaxation, and some reviews regarding endothelial dysfunction in diabetes have been published. These reviews have focused on factors that might contribute to defective relaxation, some of which will not be addressed in detail in this review. The purpose of the present review is to summarize evidence that specifically supports either decreased NO production by diabetic vascular endothelium and/or impaired NO-mediated endothelium-dependent relaxation. Second, this review provides reasonable alternatives to explain some of the controversies in this research area. Third, since there is growing evidence that arginine appears to have some benefits for diabetes-associated abnormalities, this review summarizes the current state of knowledge of effects of acute and chronic administration of L-arginine on diabetesinduced endothelial dysfunction and discusses potential NOdependent and -independent mechanisms whereby therapeutic intervention with L-arginine might benefit the diabetic endothelium.

Model studies of leukocyte-endothelium-blood interactions: II. Hemodynamic impact of leukocytes adherent to the wall of post-capillary vessels

Computational fluid dynamics (CFD) and large scale model experiments were used to analyze the hemodynamic impact of leukocytes adherent to the wall of post-capillary venules. Using a large scale model and, with the aid of a finite element package, solving the Navier Stokes equations for low Reynolds number flow in a cylinder past an adherent sphere, we have developed a dimensionless correlation which permits the estimation of the pressure drop across an adherent leukocyte in an in vivo vessel. This relationship is: f ⋅ Re ⁡ = exp ⁡ [ 2.877 + 4.630 ( d D ) 4 ] where f is the Fanning friction factor, Re is the Reynolds number and d/D is the leukocyte to vessel diameter ratio. The friction factor is proportional to the pressure drop across the leukocyte, and does not significantly increase until d/D is greater than 0.5, and then increases rapidly with increasing d/D. Computations indicate that the length of the disturbed flow region generated by an adherent leukocyte increases with decreasing vessel size. The average wall stress in the disturbed flow region remains constant, and equal to the wall stress in the undisturbed region for d/D less than approximately 0.5. For d/D greater than 0.5, the average wall stress in the disturbed flow region increases rapidly with increasing d/D. There is an even larger increase, up to five times greater than the average disturbed stress, in the peak wall stress in the disturbed flow region. This indicates that significant wall stress gradients can be generated by an adherent leukocyte in post-capillary size vessels. © 1997 Elsevier Science Ltd

Leuprolide acetate treatment and myoma arterial size

To compare the size of arterial vessels in myomas from women treated with GnRH agonist (GnRH-a) or given placebo. Our study group included 46 women about to undergo myomectomy or hysterectomy; 30 were treated with leuprolide acetate (3.75 or 7.5 mg) in three monthly doses, and 16 were given placebo. Arterial diameters of the intramyomatous vessels were measured using an ocular micrometer on hematoxylin and eosin-stained slides. Clinically and radiologically, the uterine volume of GnRH-a-treated patients decreased by an average of 30%, and the diameter of the largest myoma decreased by 27%. The average diameter of intramyomatous arteries was 24% smaller in GnRH-a subjects compared with those receiving placebo (136 +/- 42 versus 178 +/- 60 microns, P < .01). In addition, arteriosclerotic changes, including intimal and medial fibrosis, were seen more often in the GnRH-a-treated subjects (48 versus 25%, P < .05). Intramyomatous arteries were smaller and more often showed arteriosclerotic changes in leiomyomas removed from women treated with GnRH-a compared with those given placebo. The estrogen deprivation induced by GnRH-a may cause a relative vasoconstriction of myomatous vessels. Whether this decreased vessel size is the principal contributor to decreased myoma size will require further study.

Heterogeneous histochemical reaction pattern of the lectin Bandeiraea (Griffonia) simplicifolia with blood vessels of human full-term placenta

Bandeiraea simplicifolia lectin (BS-I) stains vascular endothelium in various species. In humans, less than 10% of the specimens studied exhibit a reaction with BS-I. In the present histochemical study, the reactivity of BS-I with placental blood vessels and its correlation with the blood group from mother and newborn child was investigated. Acetone-fixed cryosections of representative tissue segments of human full-term placenta and umbilical cord were stained with BS-I. The staining pattern of tissues from patients with different blood groups was identical, although the reaction of BS-I in the placenta was heterogeneous. BS-I did not react with the umbilical cord. Vascular smooth muscle cells at the insertion site of the umbilical cord into the chorionic plate, and endothelium deeper in the chorionic plate, became progressively stained. The endothelial cells and tunica muscularis of smaller arteries and veins in stem villi lost their reactivity in parallel with decreasing vessel size. Arterioles and venules reacted heterogeneously. Capillaries, trophoblastic basement membranes, especially epithelial plates, and sometimes the syncytiotrophoblast were labelled in several terminal villi. The data indicate that 1) the placenta binds BS-I to fetal endothelium independent of the blood group, 2) cell-surface antigens on placental endothelial cells are expressed heterogeneously and 3) cell-surface glycans are constituted in an organ-specific manner on human endothelial cells.

Adenylate cyclase‐mediated vascular responses of rabbit aorta, mesenteric artery and skin microcirculation

1. The importance of adenylate cyclase-mediated vascular relaxation in the macro and microcirculation was assessed in rabbit aortic and coeliac artery bioassay rings in vitro and skin microvessels in vivo. 2. The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38), the beta-agonist, isoprenaline, and the prostaglandins, PGE1 and PGE2, were compared with the activity of nitroprusside, which acts by stimulating guanylate cyclase. 3. In aortic tissue the relative relaxant potencies were (-log M EC50, 100% = response to nitroprusside 10(-6) M): nitroprusside 7.0, PACAP38 6.8, isoprenaline 6.3; PGE1 and PGE2 were weak constrictors. In coeliac artery rings relative potencies were (-log M EC50, 100% = response to nitroprusside 10(-5) M): PACAP38 6.6, PGE1 6.6, nitroprusside 6.5, PGE2 4.9, and isoprenaline 4.3. 4. Comparative potencies when injected into anaesthetized rabbit skin in vivo were (-log mol/site required to increase blood red cell flux by 75%): PACAP38 13.0, PGE2 10.7, isoprenaline 9.7, PGE1 9.1, nitroprusside < 7. 5. Nitroprusside, the most effective relaxant tested in the aorta, was 10(7) fold less potent than PACAP in its effect on skin blood flow. PGE1 and PGE2 were constrictors of the aorta, of intermediate effect in the coeliac artery, but potent vasodilators of the microcirculation. 6. In this model, the importance of adenylate cyclase-mediated vascular relaxation increases with decreasing vessel size.

Myogenic response gradient in an arteriolar network.

Experiments were conducted to test the hypothesis that a longitudinal gradient in myogenic responsiveness exists within an arteriolar network. Single arterioles were dissected from the hamster cheek pouch, cannulated with micropipettes, and transferred to an inverted microscope for in vitro study. Pressure-diameter relationships of five branching orders of arterial vessels were measured in the presence of spontaneous vascular tone and after elimination of tone with a Ca(2+)-free solution containing nitroprusside. At luminal pressures matching those found in vivo, the diameters of the vessels with spontaneous tone were as follows: small arteries, 81 microns; first-order arterioles, 52 microns; second-order arterioles, 32 microns; third-order arterioles, 24 microns; and fourth-order arterioles, 11 microns. All branching orders of vessels exhibited true myogenic responses as indicated by negative slopes of their pressure-diameter relationships. Each vascular branching order exhibited its maximum myogenic responsiveness at a pressure near or just slightly higher than its normal pressure as measured in vivo. Relative myogenic responsiveness increased with decreasing vessel size down to the level of the second- and third-order arterioles, whereas fourth-order arterioles were substantially less responsive than third-order arterioles. A compilation of data from numerous in vivo and in vitro studies suggests that the same myogenic response pattern may be found in other vascular beds.