Differential effects of prostaglandins A1 and A2 on pulmonary vascular resistance in the dog.

The effects of PGA1 and PGA2 were studied in the canine pulmonary vascular bed. Infusion of PGA1 into the lobar artery decreased lobar arterial and venous pressure but did not change left atrial pressure. In contrast, PGA2 infusion increased lobar arterial and venous pressure and the effects of this substance were similar in experiments in which the lung was perfused with dextran or with blood. These data indicate that under conditions of controlled blood flow PGA1 decreases pulmonary vascular resistance by dilating intrapulmonary veins and to a lesser extent vessels upstream to the small veins, presumably small arteries. The present data show that PGA2 increases pulmonary vascular resistance by constricting intrapulmonary veins and upstream vessels. The predominant effect of PGA2 was on upstream vessels and the pressor effect was not due to interaction with formed elements in the blood or platelet aggregation.     

Effect of taurine on the microvessel exchange function and adrenergic response of veins and arteries in the cat skeletal muscle

In cats anesthetized with Uretan and perfused with a constant blood volume, Taurine induced responses of neither arterial nor venous vessels of the skeletal muscle but increased the capillary filtration coefficient without any significant change of the capillary pressure in the skeletal muscle's microvessels. Taurine also increased both the constrictor and the dilatory responses of the arterial and venous vessels. The mechanism of the Taurine effects upon the smooth muscle elements of arteries and veins as well as upon proper mechanisms of capillary pressure control and capillary filtration coefficient, seems to be calcium-dependent.     

Occlusion pressures vs. micropipette pressures in the pulmonary circulation

Because of the discrepancies between the arterial and venous occlusion technique and the micropuncture technique in estimating pulmonary capillary pressure gradient, we compared measurements made with the two techniques in the same preparations (isolated left lower lobe of dog lung). In addition, we also obtained direct and reliable measurements of pressures in 0.9-mm arteries and veins using a retrograde catheterization technique, as well as a microvascular pressure made with the double-occlusion technique. The following conclusions were made from dog lobes perfused with autologous blood at normal flow rate of 500-600 ml/min and pressure gradient of 12 mmHg. 1) The double-occlusion technique measures pressure in the capillaries, 2) a small pressure gradient (0.5 mmHg) exists between 30- to 50-micron arteries and veins, 3) a large pressure gradient occurs in arteries and veins greater than 0.9 mm, 4) the arterial and venous occlusion techniques measure pressures in vessels that are less than 900 microns diam but greater than 50 microns, very likely close to 100 microns, 5) serotonin constricts arteries (larger and smaller than 0.9 mm) whereas histamine constricts veins (larger and smaller than 0.9 mm). Thus three different techniques (small retrograde catheter, arterial and venous occlusion, and micropuncture) show consistent results, confirming the presence of significant resistance in large arteries and veins with minimal resistance in the microcirculation.     

The vasculature of the rat penis: a scanning electron microscopic and histologic study.

As a basis for understanding the mechanism of erection in an animal model frequently used in research in reproductive biology, the angioarchitecture of the penis of the rat has been described using scanning electron microscopy. Study of the penile vasculature of the rat indicates that the corpora cavernosa penis and the corpus spongiosum are independent erectile tissues, each with its own arterial and venous vessels. The large vascular spaces and abundant smooth muscle of the penile crura are compatible with its role in regulating blood flow to more distal penile tissues. Helicine arteries of the crura, but not the parent deep penile artery or arteries elsewhere, have muscular cushions in their walls. The venous drainage of the penile crura is via subtunical veins which are thought to be compressed during erection to elevate pressure within the penis. Large, paired cavernous veins drain the shaft of the penis. A unique method for inhibiting blood flow from the penis is indicated by the division of the cavernous veins into smaller channels prior to joining the subtunical venous plexus. Erectile tissue in the bifid origins of the corpus spongiosum has abundant cavernous muscle, while in the remainder of the corpus spongiosum little smooth muscle lines the cavernous spaces. The cavernous spaces on either side of the urethra coalesce to form vessels, each of which communicates with cavernous spaces in the glans. In addition, a bypass of the glans is effected by communication of these vessels directly with the deep dorsal vein. The apparent absence of muscular pads in vessels of the spongiosum, the relative paucity of cavernous smooth muscle, and the ample venous drainage provided by the deep dorsal vein may account for the lack of a venous occlusive mechanism similar to that of the corpora cavernosa penis.     

Increased resistance in postobstructive pulmonary vasculopathy: structure-function relationships

Postobstructive pulmonary vasculopathy (POPV) was produced by chronic ligation (120 days) of the left main pulmonary artery of seven dogs. To explain the abnormal physiological changes found using arterial and venous occlusion (AVO) in POPV (J. Appl. Physiol. 69: 1022-1032, 1990), the light-microscopic morphology, morphometry (n = 5), and ultrastructure (n = 6) of ligated left lower lobes were compared with contralateral control right lower lobes. First, there was a proliferation of bronchial vessels around pulmonary vessels and airways to explain bronchial blood flow rates of 330 ml/min in left lower lobes. The walls of the bronchial vessels contained smooth muscle with minimal elastic tissue and prominent myoendothelial junctions. Second, focal bronchopulmonary anastomoses were seen in pulmonary arteries approximately equal to 100 microns diam, which is consistent with our conclusion that the major site of communication is at the precapillary level and suggests that the limit between arterial and middle segments defined by AVO may lie in arteries of approximately equal to 100 microns. Third, to explain the increased arterial resistance in POPV, the pulmonary arteries had an increased percent medial muscle thickness, peripheral muscularization, and focal intimal thickening but had no plexiform lesions. The ultrastructure of the arteries revealed new intimal cells and numerous myoendothelial junctions rarely found in controls. Capillaries and veins were only subtly altered. Fourth, the hyperreactivity of arteries to serotonin and of veins to histamine found using AVO was partially explained by the increased medial thickness and decreased diameter but may also be due to increased receptor concentration or related to the myoendothelial junctions. We conclude that most of the hemodynamic alterations in POPV are related to morphological abnormalities and that this model has clinical and experimental relevance in the study of bronchopulmonary vascular interactions.     

Dynamics of human cardiovascular responses in different periods of long-term exposure to weightlessness

The purpose of this work was to determine the dynamics of changes in the state of the human cardiovascular system at rest and upon exposure to lower body negative pressure (LBNP) in different periods of short-term (8?C25 days) and long-term (126?C438 days) space flights (SFs) using the data of ultrasonic examinations and leg occlusive plethysmography. It was established that the changes caused by blood redistribution and hypovolemia development??a decreased left-ventricular filling and stroke volume without an impairment of myocardial contractility, a decreased renal artery resistance, and an increased maximal capacity of leg veins??occurred in the first week of an SF. Over 30?C40 days of SF, these changes increased and were followed by the relative stabilization of hemodynamics at rest. Arterial cerebral blood flow was stable; however, the phenomena of venous congestion in this region increased with the SF??s duration. The most dramatic changes were observed in leg vessels, both in arteries (decreased resistance) and veins (increase in maximum capacity). Changes in the venous part of the cardiovascular system were more marked than in the arterial one. Despite the relative stabilization of the hemodynamics at rest, exposure to LBNP revealed a deterioration of gravity-dependent reactions, which changed as a function of the SF duration. In the first month of FS, the downward trend of the femoral artery vasoconstriction was not detrimental to cerebral blood flow. SF extension impaired the regulation of the vascular tone and caused increased blood flow deficiency on exposure to LBNP. In some cases, the hemodynamic response was affected to the extent that could be regarded as a failure to adapt to orthostatic effects.     

Physiological and immunocytochemical evidence for a new concept of blood flow regulation in the corpus luteum

To explain the high rate of blood flow in the corpus luteum, we hypothesize that luteal blood vessels offer minimal resistance to flow and are incapable of vasomotion. This hypothesis was tested in rabbits at mid-pseudopregnancy by measuring blood flow in the corpus luteum and ovarian stroma with tracer-labeled microspheres at three levels of arterial blood pressure, which was manipulated by constricting the aorta above the ovarian artery. In addition, the distribution of vascular smooth muscle in the ovary was evaluated with morphological and immunocytochemical techniques. Decreases in arterial pressure were paralleled by reductions in blood flow in the corpus luteum, whereas ovarian stromal blood flow was unchanged. Consistent with our hypothesis, there was no change in the low level of vascular resistance offered by blood vessels in the corpus luteum, supporting the view that they are maximally dilated and incapable of autoregulation. Morphologically, the vessels within the corpus luteum appeared as large sinusoidal capillaries without smooth muscle, providing an anatomical explanation for the lack of vasomotor control demonstrated physiologically. The absence of vascular smooth muscle was confirmed with immunocytochemistry using an antibody against the muscle-specific intermediate filament, desmin. The fluorescein-labeled antibody decorated arteries and arterioles within the ovarian stroma and near the capsule of the corpus luteum, but did not decorate vessels in the corpus luteum of pseudopregnancy, providing additional evidence that the vessels of the corpus luteum lack the smooth muscle investment necessary to change vascular caliber. From these findings, we have proposed a novel scheme to explain intraovarian blood flow regulation. Vascular resistance in the ovarian stroma, as in most tissues, is acutely regulated by dilation or constriction of intratissue arterioles. In contrast, vascular resistance within the corpus luteum is modeled as a relatively invariable parameter, fixed at a low level by the morphological characteristics of the luteal vasculature. Therefore, the corpus luteum operates on a linear (maximally "vasodilated") pressure-flow curve, does not actively regulate intratissue blood flow, and is subject to acute regulation of perfusion only through changes in extra-luteal vessels.     

Comparison of the effects of prostaglandins F1alpha, F2alpha, F1beta, and F2beta on the canine pulmonary vascular bed.

The effects of four F series prostaglandins on the pulmonary vascular bed were compared under conditions of controlled pulmonary blood flow in the intact spontaneously breathing dog. PGF1alpha and PGF2alpha increased lobar arterial pressure whereas PGF1beta and PGF2beta had little if any effect when infused into the lobar artery. The increase in lobar arterial pressure in response to PGF1alpha and PGF2alpha was associated with a significant increase in lobar venous pressure but no change in left atrial pressure. These data indicate that PGF1alpha and PGF2alpha increase pulmonary vascular resistance by constricting lobar veins and vessels upstream to small veins, presumed to be small arteries. It is concluded that in the pulmonary vascular bed the configuration of the hydroxyl group at carbon 9 is an important determinant of pressor activity.     

Venous responses to hypoxemia in the fetal lamb

The factors regulating umbilical venous return and its distribution between the ductus venosus and liver are poorly understood. This study was designed to determine where the major changes in resistance to umbilical venous return occur in response to fetal hypoxemia. In eight chronically-instrumented fetal lambs, during control and hypoxemic periods, we measured pressure in the descending aorta, extra-abdominal umbilical vein, portal sinus, and inferior vena cava; we also measured blood flow using radionuclide-labeled microspheres. During the control period, the umbilical arteries and placental vasculature accounted for 82% of total resistance to umbilical-placental blood flow, the umbilical veins for 11%, and the ductus venosus and liver for 7%. Hypoxemia increased resistance in the umbilical veins more than twofold, but did not affect resistance in the umbilical arteries or placenta. Although combined liver/ductus venosus resistance did not change, hepatic vascular resistance increased, and ductus venosus resistance decreased. We conclude that the major increase in resistance to umbilical venous return in response to hypoxemia resides in the umbilical veins. This increased resistance may improve maternal-fetal blood gas exchange by increasing the fetal surface area in the placenta.     

Localization of the sites of pulmonary vasomotion by use of arterial and venous occlusion

In this study, we present a new approach for using the pressure vs. time data obtained after various vascular occlusion maneuvers in pump-perfused lungs to gain insight into the longitudinal distribution of vascular resistance with respect to vascular compliance. Occlusion data were obtained from isolated dog lung lobes under normal control conditions, during hypoxia, and during histamine or serotonin infusion. The data used in the analysis include the slope of the arterial pressure curve and the zero time intercept of the extrapolated venous pressure curve after venous occlusion, the equilibrium pressure after simultaneous occlusion of both the arterial inflow and venous outflow, and the area bounded by equilibrium pressure and the arterial pressure curve after arterial occlusion. We analyzed these data by use of a compartmental model in which the vascular bed is represented by three parallel compliances separated by two series resistances, and each of the three compliances and the two resistances can be identified. To interpret the model parameters, we view the large arteries and veins as mainly compliance vessels and the small arteries and veins as mainly resistance vessels. The capillary bed is viewed as having a high compliance, and any capillary resistance is included in the two series resistances. With this view in mind, the results are consistent with the major response to serotonin infusion being constriction of large and small arteries (a decrease in arterial compliance and an increase in arterial resistance), the major response to histamine infusion being constriction of small and large veins (an increase in venous resistance and a decrease in venous compliance), and the major response to hypoxia being constriction of the small arteries (an increase in arterial resistance). The results suggest that this approach may have utility for evaluation of the sites of action of pulmonary vasomotor stimuli.     

Tibial nerve and deep fibular nerve effects on venous and extravascular volumes

The innervation of the vasculature of the dog hindpaw separately controls the series and parallel coupled vessels by means of the tibial, deep fibular, and superficial fibular nerves. The latter primarily affects veins. The venous effects of the tibial and deep fibular nerves have not been adequately defined. The right hindpaw of anesthetized dogs was vascularly and neurally isolated in a volume recorder. The animals were heparinized and the preparation autoperfused (constant pressure). Total tissue volume changes were determined by the volume recorder. Total vascular volume changes were calculated from changes in paw 51Cr-red blood cell radioactivity measured by a scintillation detector. Arterial pressure and paw blood flow were monitored. The tibial and deep fibular nerves were each separately stimulated at 1, 5, and 15 Hz. Deep fibular nerve stimulations resulted in progressively significant increases in precapillary flow resistance. Vascular and tissue volumes decreased with stimulation frequency but vascular volume decreased significantly less than tissue volume change. Tibial nerve stimulation resulted in significant precapillary resistance increases. Vascular and tissue volumes decreased by similar amounts. Thus, deep fibular nerve stimulation causes passive decrease in venous volume, reduced capillary pressure, and fluid absorption. Tibial nerve stimulation causes active arterial and venous constriction maintaining capillary pressure with minimal fluid transfer.     

Effect of hypoxia on pulmonary blood flow-segmental vascular resistance relationship in perfused cat lungs

To investigate the effect of alveolar hypoxia onthe pulmonary blood flow-segmental vascular resistance relationship, wedetermined the longitudinal distribution of vascular resistance whileincreasing blood flow during hyperoxia or hypoxia in perfused catlungs. We measured microvascular pressures by the micropipetteservo-null method, partitioned the pulmonary vessels into threesegments [i.e., arterial (from main pulmonary artery to 30- to50-µm arterioles), venous (from 30- to 50-µm venules to leftatrium), and microvascular (between arterioles and venules)segments] and calculated segmental vascular resistance. Duringhyperoxia, total resistance decreased with increased blood flow becauseof a reduction of microvascular resistance. In contrast, duringhypoxia, not only microvascular resistance but also arterial resistancedecreased with increase of blood flow while venous resistance remainedunchanged. The reduction of arterial resistance was presumably causedby arterial distension induced by an elevated arterial pressure duringhypoxia. We conclude that, during hypoxia, both microvessels andarteries >50 µm in diameter play a role in preventing furtherincreases in total pulmonary vascular resistance with increased bloodflow.

     

Prostacycin production by arterialized autogenous venous grafts in dogs

Arteries are capable of producing significantly larger quantities of protacyclin than are veins. To test the hypothesis, whether prostacyclin production by the vessel wall is related to blood pressure and flow, we measured the amounts of PGI₂ released and synthesized by venous segments transplanted for 6 weeks into the arterial circulation. These results were compared with the production of prostacyclin by normal veins and arteries. In 20 dogs a segment of jugular vein was interposed into the carotid system; a sham dissection was done on the opposite side. “Arterialized” vein grafts showed prominent intima lined by endothelium, medial smooth muscle cell proliferation and fibrotic proliferation in adventitia. Spontaneous and arachidonic acid- stimulated prostacyclin production (measured by radioimmunoassay for 6-keto-PGF_1α) was not significantly different between arterialized venous autografts and jugular veins. Significantly larger amounts of prostacyclin were synthesized by the carotid artery. Thus, histologic changes and rheologic effects occurring in vein grafts transposed to the arterial site do not affect prostacyclin production.     

Vascular anatomy of the lateral musculature of the flathead,Platycephalus bassensis (Teleostei: Perciformes)

Summary The vascular anatomy of the lateral musculature of the flatheadPlatycephalus bassensis, was studied by scanning electron microscopy of corrosion casts. Arteries and veins showed an alternating pattern in neighbouring vertebral segments. The red muscle was supplied by five major branches of the intermuscular artery, and the white muscle by infrequent branches of the intermuscular artery, dorsal segmental artery and ventral segmental artery. Venous drainage of the red and white muscles broadly mimicked the arterial supply. The functional unit of the trunk vasculature can be considered as an artery, a vein and connecting fine blood vessels. There appear to be 2 over-lapping types leading to alternating clockwise and counter-clockwise flows of blood. Small satellite vessels were observed running parallel to most of the larger blood vessels. No anatomical A-V shunt vessels, or series vascular connections between the red and white muscle, were observed. The irregular, alternating adult system is postulated to have developed from an earlier system showing strict bilateral symmetry and equal arterial and venous development in each vertebral segment.     

Theoretical model of blood flow autoregulation: roles of myogenic, shear-dependent, and metabolic responses

The autoregulation of blood flow, the maintenance of almost constant blood flow in the face of variations in arterial pressure, is characteristic of many tissue types. Here, contributions to the autoregulation of pressure-dependent, shear stress-dependent, and metabolic vasoactive responses are analyzed using a theoretical model. Seven segments, connected in series, represent classes of vessels: arteries, large arterioles, small arterioles, capillaries, small venules, large venules, and veins. The large and small arterioles respond actively to local changes in pressure and wall shear stress and to the downstream metabolic state communicated via conducted responses. All other segments are considered fixed resistances. The myogenic, shear-dependent, and metabolic responses of the arteriolar segments are represented by a theoretical model based on experimental data from isolated vessels. To assess autoregulation, the predicted flow at an arterial pressure of 130 mmHg is compared with that at 80 mmHg. If the degree of vascular smooth muscle activation is held constant at 0.5, there is a fivefold increase in blood flow. When myogenic variation of tone is included, flow increases by a factor of 1.66 over the same pressure range, indicating weak autoregulation. The inclusion of both myogenic and shear-dependent responses results in an increase in flow by a factor of 2.43. A further addition of the metabolic response produces strong autoregulation with flow increasing by a factor of 1.18 and gives results consistent with experimental observation. The model results indicate that the combined effects of myogenic and metabolic regulation overcome the vasodilatory effect of the shear response and lead to the autoregulation of blood flow.     

Status of the "dead point" of blood flow in anastomoses of superficial cerebral arteries as affected by an acute increase of blood pressure

Changes in pial arteries diameter and the condition of blood flow "dead point" in arterial anastomoses were established using the brain window during an acute increase of mean arterial pressure (MAP) induced by intravenous injection of norepinephrine (NE) with microcineangiography and the analysis of films and frames on a montage table and TAS ("Leitz"). During an acute increase of MAP the movement of blood flow "dead point" in anastomoses and the expansion of plasma segments occurred much more frequently than in normotension. The stabilization of blood flow "dead point" was observed at high constant MAP. Pronounced dilation of both pial arteries and veins first occurred in anastomoses, then spread to arterial branches. It is assumed that high vulnerability of the brain vessels of the borderline zones is due to breakthrough in autoregulation of cerebral blood flow on its upper limit and depends on the repeatedly changing directions of the blood flow and its moving "dead point", as the peripheral resistance of arterial anastomoses-forming branches under these circumstances changes in an irregular manner.     

The study of cerebral venous blood flow disturbance peculiarity in the norm and under the extravasal compression of brachiocephalic veins with the use of magnetic resonance venography and ultrasound duplex scanning

The MR-venography of the veins and brain venous sinuses, brachiocephalic veins an internal jugular veins duplex scanning have been performed in order to study the distinctions of cerebral venous hemodynamics of healthy people and the patients with venous encephalopathy caused by the extravasal compression of the brachiocephalic veins at the neck level and the superior sections of mediastinum. It has been revealed that the blood flow reducing in transverse brain sinuses occurs not only in the case of outflow disorder in the distal sections of the venous system, but also in norm. This reducing depends on anatomic constitution of confluens sinuum and the venous angle type of brachiocephalic veins. The three venous angle types of brachiocephalic veins have been distinguished: y-type, mu-type and Y-type. It has been registered that in case of the mu-type angle the blood flow can be reduced in norm due to peripheral resistance increase at the physiological bends of nearly a right angle type. The distinctions of hemodynamics in case of venous obstruction in contrast to arterial obstruction have been described. It has been registered that in case of outflow trouble in one of the internal jugular veins the speed and the volume of the blood flow in it are progressively reduced depending on the duration and the manifestation of compression. All this results in narrowing of the vein diameter from the affected side, and in compensatory distention of the diameter and increase of blood flow volume in the contralateral internal jugular vein, vertebral and external jugular veins, in succession.     

Bifurcation asymmetry of the porcine coronary vasculature and its implications on coronary flow heterogeneity

The branching pattern of the coronary arteries and veins is asymmetric, i.e., many small vessels branch off of a large trunk such that the two daughter vessels at a bifurcation are of unequal diameters and lengths. One important implication of the geometric vascular asymmetry is the dispersion of blood flow at a bifurcation, which leads to large spatial heterogeneity of myocardial blood flow. To document the asymmetric branching pattern of the coronary vessels, we computed an asymmetry ratio for the diameters and lengths of all vessels, defined as the ratio of the daughter diameters and lengths, respectively. Previous data from silicone elastomer cast of the entire coronary vasculature including arteries, arterioles, venules, and veins were analyzed. Data on smaller vessels were obtained from histological specimens by optical sectioning, whereas data on larger vessels were obtained from vascular casts. Asymmetry ratios for vascular areas, volumes, resistances, and flows of the various daughter vessels were computed from the asymmetry ratios of diameters and lengths for every order of mother vessel. The results show that the largest orders of arterial and venous vessels are most asymmetric and the degree of asymmetry decreases toward the smaller vessels. Furthermore, the diameter asymmetry at a bifurcation is significantly larger for the coronary veins (1.7-6.8 for sinus veins) than the corresponding arteries (1.5-5.8 for left anterior descending coronary artery) for orders 2-10, respectively. The reported diameter asymmetry at a bifurcation leads to significant heterogeneity of blood flow at a bifurcation. Hence, the present data quantify the dispersion of blood flow at a bifurcation and are essential for understanding flow heterogeneity in the coronary circulation.     

Absence of venous valves in mice lacking Connexin37

Venous valves play a crucial role in blood circulation, promoting the one-way movement of blood from superficial and deep veins towards the heart. By preventing retrograde flow, venous valves spare capillaries and venules from being subjected to damaging elevations in pressure, especially during skeletal muscle contraction. Pathologically, valvular incompetence or absence of valves are common features of venous disorders such as chronic venous insufficiency and varicose veins. The underlying causes of these conditions are not well understood, but congenital venous valve aplasia or agenesis may play a role in some cases. Despite progress in the study of cardiac and lymphatic valve morphogenesis, the molecular mechanisms controlling the development and maintenance of venous valves remain poorly understood. Here, we show that in valved veins of the mouse, three gap junction proteins (Connexins, Cxs), Cx37, Cx43, and Cx47, are expressed exclusively in the valves in a highly polarized fashion, with Cx43 on the upstream side of the valve leaflet and Cx37 on the downstream side. Surprisingly, Cx43 expression is strongly induced in the non-valve venous endothelium in superficial veins following wounding of the overlying skin. Moreover, we show that in Cx37-deficient mice, venous valves are entirely absent. Thus, Cx37, a protein involved in cell–cell communication, is one of only a few proteins identified so far as critical for the development or maintenance of venous valves. Because Cxs are necessary for the development of valves in lymphatic vessels as well, our results support the notion of common molecular pathways controlling valve development in veins and lymphatic vessels.     

The blood-brain barrier: an alternative hypothesis

Brain blood vessels, unlike most vessels elsewhere in the body, exhibit a blood-brain barrier (BBB) to certain substances, e.g. trypan blue. Under some circumstances this barrier is no longer effective and the permeability of the vessels increases. Although capillarization is much less in the brain than in many other organs, e.g. heart muscle, total cerebral blood flow per minute is enormous. Consequently, to accommodate a large blood volume with a limited capillary bed, the velocity of blood through brain vessels must be extremely fast. The hypothesis presented in this paper is that this rapid flow results in a low or negative pressure on the endothelium, and plasma and trypan blue are prevented from passing through the wall. The tight junctions of cerebral endothelial cells may be able to withstand only a limited amount of pressure on their luminal surface. If the velocity of blood in brain capillaries decreases, pressure on the endothelium should increase, and brain vessels, like blood vessels elsewhere in the body, become permeable to vital dyes. Other conditions also increase capillary permeability, e.g. acute arterial hypertension or venous congestion. Although brain vessels can adapt to a moderate, gradual change in systemic pressure, when a significant rise in cerebral arterial pressure is abrupt, the compensatory changes in the postcapillary venous bed may be inadequate and consequently intracapillary pressure and vascular permeability are increased. Venous congestion increases intracapillary pressure by restricting capillary outflow as well as by reducing velocity through capillary beds. Under such conditions increased capillary permeability may be indicated by cerebral edema, and even, on occasion, by petechial hemorrhages. In short, if the flow is fast and unimpeded the BBB will be effective; if the velocity decreases, or intracapillary pressure increases for whatever reason, the permeability of the brain endothelium will be abnormally increased.