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T C Skalak

Publications and source records attributed to T C Skalak.

At least 19 recordsLinked to original sources
PubMed2000

Role of leukocytes and tissue-derived oxidants in short-term skeletal muscle ischemia-reperfusion injury.

The relative contribution of xanthine oxidase (XO) and leukocytes to tissue injury after short-term ischemia is unknown. In this study, we subjected three groups of rat spinotrapezius muscles to 30-min ischemia and 1-h reperfusion: 1) ischemia-reperfusion (I/R) + 0.9% saline, 2) I/R + superoxide dismutase, and 3) I/R + oxypurinol. A fourth group served as nonischemic control. We quantified the increase in resistance (%DeltaR) caused by leukocyte-capillary plugging concurrently with myocyte uptake of propidium iodide (PI) [expressed as no. of PI spots per total volume of perfused tissue (N(PI)/V)] and performed assays to quantify XO activity, thiobarbituric acid-reactive substances (TBARS), and myeloperoxidase (MPO). Groups 2 and 3 exhibited significant decreases in N(PI)/V relative to group 1. MPO levels and TBARS were similar among all groups, and mean %DeltaR was significantly reduced in groups 2 and 3 relative to group 1. However, elevated XO was observed in groups 1 and 2 relative to group 3 and nonischemic controls. These data are consistent with the hypothesis that XO, rather than toxic species produced by plugging or venule-adherent leukocytes, is responsible for postischemic damage in this model.

Animals↗
PubMed1998

Spontaneous redistribution after reperfusion: a unique property of AIP 201, an ultrasound contrast agent.

OBJECTIVES: We sought to determine the mechanism of spontaneous redistribution of AIP 201 microbubbles after reperfusion from a single left heart injection performed during coronary occlusion. BACKGROUND: AIP 201, an ultrasound contrast agent consisting of 10-microm sized microbubbles, has demonstrated spontaneous myocardial redistribution in preliminary studies. METHODS: Myocardial video intensity (VI) and radiolabeled microsphere-derived myocardial blood flow (MBF) were measured serially after reperfusion in seven dogs undergoing an AIP 201 injection during coronary occlusion. The behavior of these bubbles was also assessed in the rat spinotrapezius muscle using intravital microscopy (IM), both with and without ultrasound. The effect of ultrasound on these bubbles was also determined in vitro. RESULTS: A spontaneous and gradual increase in myocardial VI was noted after reperfusion, which was related to the magnitude of increase in MBF to that region (r=0.82, p < 0.001). On IM, most of the microbubbles were seen entrapped in small arterioles. Some larger arterioles had aggregates of microbubbles that periodically became dislodged and moved downstream. This behavior was not affected in vivo by ultrasound. In vitro, however, microbubble aggregation was noted only during ultrasound exposure. CONCLUSIONS: The magnitude of redistribution of AIP 201 microbubbles to the reperfused myocardium is related to changes in MBF and occurs from their dislodgement from microbubble aggregates entrapped in large arterioles. In vitro microbubble aggregation seen during ultrasound exposure was not reproduced in vivo. These results may have important implications for studying the effects of interventions in acute coronary syndromes and after coronary artery bypass graft surgery.

Animals↗
PubMed1998

Delivery of colloidal particles and red blood cells to tissue through microvessel ruptures created by targeted microbubble destruction with ultrasound.

BACKGROUND: We have previously shown that the application of ultrasound to thin-shelled microbubbles flowing through small microvessels (<7 microm in diameter) produces vessel wall ruptures in vivo. Because many intravascular drug- and gene-delivery vehicles are limited by the endothelial barrier, we hypothesized that this phenomenon could be used to deliver drug-bearing vehicles to tissue. METHODS AND RESULTS: An exteriorized rat spinotrapezius muscle preparation was used. Intravascular fluorescent red blood cells and polymer microspheres (PM) (205 and 503 nm in diameter) were delivered to the interstitium of rat skeletal muscle through microvessel ruptures created by insonifying microbubbles in vivo. On intravital microscopy, mean dispersion areas per rupture for red blood cells, 503-nm PM, and 205-nm PM were 14.5x10(3) microm2, 24. 2x10(3) microm2, and 27.2x10(3) microm2, respectively. PM dispersion areas were significantly larger than the mean dispersion area for red blood cells (P<0.05). CONCLUSIONS: Microvessel ruptures caused by insonification of microbubbles in vivo may provide a minimally invasive means for delivering colloidal particles and engineered red blood cells across the endothelial lining of a targeted tissue region.

Animals↗
PubMed1998

Direct in vivo visualization of intravascular destruction of microbubbles by ultrasound and its local effects on tissue.

BACKGROUND: Our aim was to observe ultrasound-induced intravascular microbubble destruction in vivo and to characterize any resultant bioeffects. METHODS AND RESULTS: Intravital microscopy was used to visualize the spinotrapezius muscle in 15 rats during ultrasound delivery. Microbubble destruction during ultrasound exposure caused rupture of < or = 7-microm microvessels (mostly capillaries) and the production of nonviable cells in adjacent tissue. The number of microvessels ruptured and cells damaged correlated linearly (P<0.001) with the amount of ultrasound energy delivered. CONCLUSIONS: Microbubbles can be destroyed by ultrasound, resulting in a bioeffect that could be used for local drug delivery, angiogenesis, and vascular remodeling, or for tumor destruction.

Air↗
PubMed1998

Prazosin administration enhances proliferation of arteriolar adventitial fibroblasts.

Chronic vasodilation stimulates the formation of new arterioles in skeletal muscle, a process that requires the differentiation of mesenchymally derived precursor cells on the abluminal surface of capillaries. Fibroblast proliferation and migration to the arterializing capillary likely precede this differentiation process. In the current study, we investigated the effects of chronic vasodilation with the alpha1 adrenergic blocker prazosin, a treatment that produces enhanced terminal arteriolar development, on the proliferation of fibroblasts present in the adventitia of transverse arterioles. Dual-immunofluorescence labeling for the smooth muscle contractile protein SM-myosin heavy chain (MHC) and for bromodeoxyuridine (BRDU) uptake revealed that prazosin treatment for 4 days stimulated a threefold increase in the density of proliferating fibroblasts surrounding transverse arteriolar trees. This increase was primarily due to an eightfold increase in the density of S-phase fibroblasts surrounding <8 micron m diameter terminal arterioles and a 280% increase in the density of S-phase fibroblasts surrounding 8- to 12-micron m terminal arterioles. Alcian blue counterstaining indicated that no proliferating cells were mast cells. An in vitro study demonstrated that prazosin, at concentrations of 0.5 and 0.05 mg/liter, has no direct effect on fibroblast proliferation. It is concluded that chronic vasodilation with prazosin, a treatment that elicits elevated levels of hemodynamic stress, stimulates the proliferation of adventitial fibroblasts, particularly at the terminal endings of transverse arteriolar trees.

Adrenergic alpha-Antagonists↗
PubMed1998

Distribution of cellular proliferation in skeletal muscle transverse arterioles during maturation.

OBJECTIVE: To investigate the spatial and phenotypic origin of the new smooth muscle (SM) cells that are necessary for transverse arteriolar (TA) remodeling by establishing the distribution of cellular proliferation in TA trees during maturation. METHODS: Whole-mount gracilis muscles from rats at 4 and 9 weeks of age were immunolabeled for SM myosin heavy chain to denote arterioles and for bromodeoxyuridine to denote S-phase (DNA synthesizing) nuclei. The dimensions of each clearly visible segment in TA trees were measured. S-phase cells in the wall of, or within 5 microns of, TA segments were identified as (1) endothelium or intimal fibroblasts, (2) SM, or (3) interstitial cells. The relative percentages of each cell type in S-phase, the distribution of arteriolar diameters containing S-phase SM, and the density of S-phase interstitial cells (per unit length and per unit surface area of TA) were determined. Alcian blue counterstaining was used to discern the percentage of interstitial cells that were mast cells. RESULTS: At 4 and 9 weeks, respectively, 3.7% and 2.1% of S-phase cells were endothelium or intimal fibroblasts, 3.0% and 4.2% were SM, and 93.3% and 93.7% were interstitial cells. No S-phase interstitial cells within 5 microns of TAs were mast cells. The mean diameter of TA segments containing as S-phase SM nucleus was 15.22 +/- 1.2 microns at 4 weeks of age, with the minimum diameter being 8.9 microns. From 4 to 9 weeks of age, the number of interstitial cells per unit length of TA decreased 10-fold from 15.2 (n = 115) to 1.5 (n = 182) cells/min. At 4 weeks, the density of S-phase interstitial cells was greatest surrounding the most terminal arterioles. CONCLUSIONS: When coupled with the result that S-phase SM is absent in the most terminal segments, the relatively high density of S-phase interstitial cells surroundings the smallest diameter terminal segments at 4 weeks of age is consistent with the hypothesis that fibroblast hyperplasia is a component of terminal arteriolar development.

Animals↗
PubMed1997

Accuracy of the conductance catheter for measurement of ventricular volumes seen clinically: effects of electric field homogeneity and parallel conductance.

The conductance-volume method is an important clinical tool which allows the assessment of left ventricular function in vivo. However, the accuracy of this method is limited by the homogeneity of electric field the conductance catheter produces and the parallel conductance of surrounding structures. This paper examines these sources of error in volumes seen clinically. The characteristics of electric field within a chamber were examined using computer simulation. Nonconductive and conductive models were constructed and experimental measurements obtained using both single-field (SF) and dual-field (DF) excitation. Results from computer simulations and in vitro measurements were compared to validate the purposed theoretical model of conductance-volume method. The effects of field homogeneity and significance of parallel conductance in volume measurement were then determined. The results of this study show that DF provide a more accurate measure of intraventricular volume than SF, especially at larger volumes. However, both significantly underestimate true volume at larger volumes. In addition, the parallel conductance due to the chamber wall is significant at small volumes, but diminishes at larger volumes. Furthermore, the effect of parallel conductance beyond the chamber wall may be negligible. This study demonstrates the limitations in applying current conductance technology to patients with dilated hearts.

Animals↗
PubMed1997

Geometric resistance and microvascular network architecture of human colorectal carcinoma.

OBJECTIVE: To measure the geometric resistance to blood flow in human colorectal carcinoma. Although tumor blood flow is of central importance in both the detection and the treatment of cancer, the determinants of blood flow through the neoplastic circulation are poorly understood. METHODS: Human colorectal carcinomas (tissue weight = 272 g +/- 43 g (SD), n = 6) were perfused ex vivo with a buffered physiological salt solution of known viscosity at flow rates ranging from 2.5 to 40 ml/min and perfusion pressures from 8 to 100 mm Hg. The geometric resistance was determined from the slope of the pressure-flow curve. For examination of the principal determinant of geometric resistance, the vascular architecture, one of the tumors was perfused with Batson's No. 17 polymer and macerated in KOH to produce a positive vascular east that was used for measurement of vascular branching patterns and dimensions. RESULTS: The pressure-flow relationship was linear at perfusion pressures above 40 mm Hg, and the geometric resistance, zzero, was constant at approximately 6.5 x 10(9) g/cm3. Below 40 mm Hg, zzero increased rapidly. The architecture of the arteriolar and capillary networks of human colorectal carcinoma is similar to those of experimental rodent tumors. Capillaries in planar and nonplanar meshworks had mean segment diameters of 11 +/- 2 and 9.6 +/- 2 microns, lengths of 46 +/- 24 and 107 +/- 40 microns, and intercapillary distances of 46 +/- 13 and 74 +/- 24 microns, respectively. CONCLUSIONS: The geometric flow resistance in neoplastic tissue is 1-2 orders of magnitude higher than that observed in normal tissues. A decrease in functional vascular cross-sectional area may explain the additional increase in resistance at small perfusion pressures. The observed flow resistance may be due to the specialized arteriolar and capillary network architecture, pressure exerted by proliferating cancer cells, and/or coupling between vascular and extravascular flow. These observations demonstrate that tumor vascularity alone may not be indicative of flow resistance or tumor susceptibility to blood-borne therapeutic agents.

Adenocarcinoma↗
PubMed1996

Hemodynamic characteristics, myocardial kinetics and microvascular rheology of FS-069, a second-generation echocardiographic contrast agent capable of producing myocardial opacification from a venous injection.

OBJECTIVES: We sought to 1) study the effects of FS-069 on cardiac and systemic hemodynamic function, myocardial blood flow, left ventricular wall thickening and pulmonary gas exchange when injected intravenously; and 2) compare the myocardial kinetics and microvascular rheology of FS-069 and Albunex when injected directly into a coronary artery. BACKGROUND: FS-069 is a second-generation echocardiographic contrast agent composed of perfluoropropane-filled albumin microspheres; it is capable of consistent and reproducible myocardial opacification from a venous injection. METHODS: Nine dogs were used to study the effects of FS-069 on hemodynamic function, pulmonary gas exchange, left ventricular wall thickening and myocardial blood flow and to characterize its myocardial kinetics when injected intravenously. These dogs were also used to compare the myocardial kinetics of FS-069 with those of Albunex during intracoronary injections. Nine Sprague-Dawley rats were used to compare the microvascular rheology of these two contrast agents, and in vitro modeling was performed to assess whether the microvascular findings of FS-069 can explain its echocardiographic behavior during direct coronary injections. RESULTS: There were no effects of 30 rapid venous injections of FS-069 (every 20 s) on cardiac output; mean aortic, pulmonary or left atrial pressures; and peak positive and negative first derivative of left ventricular pressure (dP/dt). Similarly, there were no effects of this agent on radiolabeled microsphere-measured regional myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange. When injected intravenously, the myocardial transit of this agent resembled a gamma-variate form. When diluted FS-069 was injected directly into the coronary artery; however, its transit resembled the integral of gamma-variate function, with persistent myocardial opacification lasting several minutes, which was different from that of Albunex. Intravital microscopy revealed that, unlike Albunex, when no bubbles are entrapped within the microcirculation after an arterial injection, a very small fraction of the diluted, larger FS-069 microbubbles are entrapped. In vitro modeling confirmed that this small fraction of microbubbles can result in persistent myocardial opacification. CONCLUSIONS: FS-069 produces no changes in hemodynamic function, myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange when injected intravenously in large amounts. When diluted FS-069 is injected into the coronary artery, a very small fraction of the larger bubbles are entrapped within the microcirculation, resulting in a persistent contrast effect. Thus, although FS-069 is a safe intravenous echocardiographic contrast agent, it cannot provide information on myocardial blood flow when injected directly into a coronary artery.

Albumins↗
PubMed1996

Chronic alpha 1-adrenergic blockade stimulates terminal and arcade arteriolar development.

The arteriolar network undergoes structural adaptation in several physiological and pathological conditions, including exercise, maturation, hypertension, and reduced tissue perfusion due to arterial ligation. Although many physical and biochemical stimuli for arteriolar adaptation have been proposed, the individual contributions of these specific stimuli have yet to be elucidated. We tested the hypothesis that hemodynamic stress is an important determinant of growth and remodeling in the arteriolar network. An immunofluorescence, dual-labeling technique for the smooth muscle (SM) contractile proteins SM alpha-actin and SM myosin heavy chain (MHC) was used to assess terminal and arcade arteriolar (AA) remodeling in the rat gracilis muscle arteriolar network in response to chronic vasodilation, a stimulus that elevates circumferential wall stress levels in the arterioles and capillaries. SM alpha-actin, a marker of SM from the earliest stages of differentiation, was used to delineate the terminal and AAs. SM-MHC, a marker of SM in later stages of differentiation, was used to assess the relative maturity state of SM in terminal arteriolar endings. Mean percentage of SM-MHC negative terminal arteriolar endings per muscle, a measure of terminal arteriolar development, increased from 37.6 to 56.0% after 1 wk of prazosin treatment and from 36.3 to 57.6% after 2 wk of treatment. Mean number of AA segments with diameters < 15 microns increased more than threefold from 1.25 to 5.25 after 2 wk, consistent with the formation of new AA segments by the anastomoses of small-diameter terminal arterioles. Because arteriolar remodeling proceeded in a network pattern that has been shown to be consistent with a circumferential wall stress-growth rule and inconsistent with a wall shear stress-growth rule, the experimental results suggest that circumferential wall stress is a stimulus for arteriolar network remodeling.

Actins↗
PubMed1996

Effects of leukocyte capillary plugging in skeletal muscle ischemia-reperfusion injury.

The purpose of this study was to examine the relationship between increased capillary network resistance due to leukocyte capillary plugging and tissue injury following ischemia-reperfusion (I/R). After a 30-min complete ischemia in rat spinotrapezius muscle, the frequency and duration of leukocyte capillary plugging were measured throughout capillary networks and used to estimate the increase in network flow resistance for I/R alone, I/R with phalloidin (Pl), and I/R with both Pl and cytochalasin D. Propidium iodide (PI) was used to label nonviable muscle cell nuclei within the volume of tissue supplied by the capillary network, and counts were made before ischemia, immediately after reperfusion, and 1 h postreperfusion. For I/R alone and I/R + Pl there is a linear correlation between the increase in resistance (up to 29%) and the increase in the number of PI-positive nuclei during the reperfusion period. With both Pl and cytochalasin D present in the superfusate, the resistance increase was abolished and the amount of tissue damage during reperfusion was minimized. The results indicate that the increase in resistance is linearly related to the tissue damage and that a reduction of the leukocyte stiffness reduces the injury.

Animals↗
PubMed1996

The role of mechanical stresses in microvascular remodeling.

The microvasculature is an extremely adaptable structure that is capable of architectural and functional adjustments in response to multiple biochemical and mechanical stimuli. Inadequate or inappropriate adjustments often result in pathophysiology. Recent work has brought increasing recognition of the importance of microvascular remodeling in widespread disease states such as hypertension, tumor growth, diabetes, and progressive coronary artery occlusion. Much work has been done to characterize the cells and molecules with putative roles in microvascular remodeling, but little is known regarding the mechanotransduction processes that might link hemodynamic stresses such as wall shear stress and circumferential wall stress to structural and functional changes in vivo. Two primary approaches have been employed: in vitro studies that use cultured cells and allow molecular biologic analysis of signaling pathways and gene expression; and in vivo experiments aimed at understanding vessel adaptations in the intact tissue. This article reviews the structural adaptations exhibited by microvessels and the information available from in vitro and in vivo approaches. The formation of new arterioles in intact tissues is examined in detail as an example of integrative work, and the prospects for new technologies are discussed. This is a time of great opportunity for bidirectional exchange between basic in vitro advances and in vivo experimentation. This exchange will be essential in generating new understanding of the role of mechanical stresses in microvascular remodeling.

Adaptation, Physiological↗
PubMed1995

A circumferential stress-growth rule predicts arcade arteriole formation in a network model.

OBJECTIVE: To test the hypothesis that terminal arteriolar remodeling that is stimulated by elevated levels of circumferential wall stress (sigma theta) will proceed in a network pattern that gives rise to new arcade arterioles. METHODS: A network model of two interconnected skeletal muscle arterio-capillary-venous units that incorporated diameter- and hematocrit-dependent blood viscosity was constructed. After computing the control values for wall shear stresses (tau ij) and sigma theta ij, a stimulus was provided by dilating the arterioles and raising input pressure. Wall shear stresses and sigma theta ij were then recomputed. The diameters of transverse arteriolar segments with sigma theta ij greater than a sigma theta threshold were increased by an amount that was dependent on the original diameter and the difference between sigma theta ij and the sigma theta threshold. Capillaries with an intraluminal pressure greater than a specified threshold were converted to terminal arterioles. Separate simulations in which remodeling was stimulated by elevated levels of tau ij were also performed for comparison. RESULTS: Arterialization patterns from simulations of sigma theta ij stimulated arteriolar remodeling were representative of those seen in vivo with arterialization of back-connection capillaries leading to arcade arteriole formation. Simulations based on similar rules for tau ij yielded arterio-venous shunts, which are rarely seen in vivo, but no arcade arterioles. CONCLUSION: The simulations presented here are consistent with the hypothesis that arteriolar remodeling is stimulated by increased levels of circumferential wall stress and that new arcade arteriole formation is a consequence of terminal arteriolar growth.

Animals↗
PubMed1994

Circumferential wall stress as a mechanism for arteriolar rarefaction and proliferation in a network model.

Hypertension results in structural rarefaction of the microvascular arteriolar network while, conversely, decreasing pressure results in arteriolar proliferation. A remodeling mechanism capable of unifying these results remains elusive. A network model of a transverse arteriole tree was used to test whether adaptations to changes in mean circumferential wall stress (sigma theta) could produce realistic structural remodeling. Vessel diameters and network boundary pressures were assigned using experimental data, and control flows (Qij) and sigma theta ij for each vessel were calculated. Mean sigma theta ij in A2 (Strahler order) vessels (sigma m) was 6.62 x 10(4) dynes/cm2. Input pressure was increased by 35% in simulated one-kidney, one-clip (s1K1C) hypertension or decreased by 30% in simulated main feeder ligation (sMFL). Vessel diameters were adjusted iteratively until each Qij was restored, simulating autoregulation. Wall stresses decreased 15.9% for hypertension (sigma m = 5.57 x 10(4) dynes/cm2), but were elevated 60.9% for main feeder ligation (sigma m = 10.65 x 10(4) dynes/cm2), A stress-growth principle was applied, so that stresses above an upper threshold cause growth while stresses below a lower threshold cause resorption. Individual vessels with sigma theta ij < 5.24 x 10(4) dynes/cm2 were removed while new A2 segments were added to A2 vessels with sigma theta ij > 8.27 x 10(4) dynes/cm2. The network structure was adjusted until all sigma theta ij were within these stress thresholds. The number of A2s decreased 22% in s1K1C and increased 96% in sMFL in quantitative agreement with experimental data, consistent with the hypothesis that wall stress may be an important determinant of network remodeling. Arteriolar proliferation and rarefaction represent adaptations to different hemodynamic conditions, but may be governed by a common stress-growth principle.

Adaptation, Physiological↗
PubMed1994

Blood volume redistribution from a passive elastic permeable microcirculation due to hypovolemia.

We measured the variations in blood and plasma density for a cyclic hemorrhage protocol in conscious rabbits to calculate delta Vf [the volume of fluid restituted into the circulation from the time the blood volume was at its control to that after the hemorrhage of a blood volume (delta V)] and delta Vs (the volume shift from micro- to macrocirculation over the same time interval). We found that delta Vf is 7% of delta V and delta Vs 60% of delta V. They combine to reduce the effect of hemorrhage on macrovascular volume by 67% of delta V. Based on a two-resistor circulation model, the change in microcirculatory pressure (delta Pmic) from control to hemorrhage was estimated from the measured cardiac outputs and arterial and venous pressures. The computations indicate that delta Vs (or delta Vf) is linearly related to delta Pmic. With one relation fitting all data of rabbits that were conscious, infused with hexamethonium, and anesthetized with pentobarbital sodium, we concluded that the two short-term volume redistributions are not direct neural control or local regulation, but the response of a passive, permeable microcirculation to delta Pmic. From the linear relations, we obtained 0.88 ml.mmHg-1.kg-1 as the compliance of the rabbit microcirculation and 0.21 ml.min-1.mmHg-1.kg-1 as its filtration coefficient.

Animals↗
PubMed1994

Capillary hemodynamics in hemorrhagic shock and reperfusion: in vivo and model analysis.

A computer network model and in vivo measurements of microcirculatory blood flow in skeletal muscle were used to study the mechanisms responsible for low flow in hemorrhagic shock and reperfusion, with focus on the potential importance of capillary diameters and leukocyte rheology. Model flows were determined by the network pressure gradient, systemic hematocrit and leukocrit, leukocyte cytoplasmic viscosity, and vessel dimensions. After 1 h of shock (40% acute bleed) in anesthetized rabbits, pressure was reduced by 45%, hemodilution occurred, and capillary diameters decreased by 21%. The 45-50% flow reduction found experimentally in gastrocnemius muscle by laser Doppler flowmetry (LDF) and a microsphere technique matched model flow predictions with one-half of the proximal capillaries narrowed. Ringer-lactate (RL) reperfusion only partially restored control LDF flow, whereas a small-volume bolus of hypertonic saline-dextran followed by RL gave complete LDF flow recovery. The model predicted these flows for moderate hemodilution states, with the added insight that low-flow conditions are exacerbated by leukocytes only if they become activated, which is often a complication in ischemia/reperfusion.

Animals↗
PubMed1994

Immunohistochemical identification of arteriolar development using markers of smooth muscle differentiation. Evidence that capillary arterialization proceeds from terminal arterioles.

Arteriolar growth is an important event in the adaptation of normal tissues as well as in important pathologies, but the site of origin of new arterioles remains unknown. The network pattern of arteriolar development in skeletal muscle was detected by use of a new immunohistochemical technique that is based on the observation that fully differentiated (mature) vascular smooth muscle (SM) cells express both SM alpha-actin and the two myosin heavy chains (MHCs) SM-1 and SM-2, whereas less differentiated (immature) vascular SM cells do not express MHC. The anterior gracilis muscle microvasculatures of 4- and 9-week-old Sprague-Dawley rats were labeled with monoclonal antibodies to SM alpha-actin and to SM MHC. Whole transverse arteriole networks were observed, and terminal arterioles, defined as terminal segments labeled with SM alpha-actin, were classified on the basis of the presence or absence of SM MHC. A significantly different percentage of terminal arteriolar endings per network without SM MHC was observed in the two groups (66.1 +/- 17.3% for 4 weeks and 27.1 +/- 18.5% for 9 weeks), suggesting that arteriolar development is more nearly complete in the older animals. Sparsely distributed capillaries exhibited thin extensions of SM alpha-actin that crossed collecting venules and joined similar extensions from an adjacent transverse arteriole, effectively forming the basis for new arcade arterioles. SM alpha-actin and SM MHC labeling in terminal arterioles was always continuous with upstream arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗