Capacity and exchange functions of the kidney blood vessels at various leveles of venous outflow

In perfusion of the cat hemodynamically isolated kidney with a constant blood flow volume, responses of venous vessels to noradrenaline did not depend on the venous outflow pressure level and only involved a diminishing of the blood filling which distinguishes kidneys from other organs. The renal veins' capacity decreased in response to noradrenaline practically completely disappears in high values of the venous outflow pressure. The renal capillary filtration coefficient was shown to equal 0.21 +/- 0.11, whereas the effect of changes in renal vein's pressure on implementation of the microvessels' exchange function in determined by the shifts of capillary hydrostatic pressure.     

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.     

Separation of Forearm Hemodynamics Into Skin and Muscle Components by Means of I-Epinephrine Iontophoresis

By a combination of iontophoresis of I-epinephrine into the skin of one arm and simultaneous venous occlusion plethysmography in both treated (muscle only) and untreated forearms (muscle plus skin), we examined in 16 normal volunteers forearm blood flow, capillary filtration coefficient and venous capacity at cuff pressure of 40 mm of mercury (VC₄₀) at rest, during tonic finger exercise and after interrupted repetitive finger exercise. Blood pressure did not change during the testing procedure. Forearm muscle conductance was about 60% to 70% of total conductance and was positively correlated with total conductance during rest and exercise. With standard exercises muscle conductance rises to 1½ to 2½ times resting level, and skin conductance rises to 2½ to 4½ times resting level. The capillary filtration coefficient is almost entirely in the muscle. It doubles in value with tonic exercise but decreases to half its resting value after interrupted repetitive exercise despite greatly increased conductance. Therefore, repetitive exercise-induced dissociation between conductance and filtration surface occurs in striated muscle. The mechanism is yet unknown. VC₄₀ in muscle is about 84% of total forearm VC₄₀. During tonic exercise muscle VC₄₀ was reduced, and during interrupted repetitive exercise the values for muscle and skin returned to resting values. A high correlation between muscle only and muscle-plus-skin for forearm blood flow and the identify between arms for measuring capillary filtration coefficient makes iontophoresis unnecessary for determining these values in forearm striated muscle under these experimental conditions.     

Dependence of hypoxic changes in macro- and micro-hemodynamics on the activity of adrenoreceptors in the skeletal muscle in hypothermia

Dependence of hypoxic changes of macro- and microcirculation on the activity of adrenergic receptors in the cooled organism was studied on decentralized shank of cat under perfusion with constant blood flow. After cooling of cat (to 30 degrees C) and blockade of alpha-adrenoreceptors hypoxic hypoxia (10% O2 in N2) caused (a) much greater reduction of precapillary resistance of shank, (b) more striking (by 3 times) increase of capillary filtration coefficient and (c) the increase of capillary pressure and postcapillary resistance in contrast to their decrease to hypoxia under hypothermia before alpha-blockade. Beta-adrenoreceptor blockade had no influence on the changes of the resistance and exchange function of skeletal muscle blood vessels evoked by hypoxia under cooling.     

Role of lipids in bone marrow-induced pulmonary edema

We examined the mechanism of the bone marrow-induced pulmonary edema in the isolated Ringer-perfused rabbit lung. Bone marrow administration (0.2 ml/kg body wt) increased pulmonary arterial pressure, capillary pressure, arterial resistance, and venous resistance within 2-4 min. Bone marrow also produced marked increases in lung wet weight and the capillary filtration coefficient but at later time points (90-120 min) during the perfusion. Only the triglyceride-containing lipid component of the bone marrow produced increases in pulmonary hemodynamics, lung wet weight, and the capillary filtration coefficient comparable to those observed after bone marrow. Bone marrow and the lipid component of bone marrow both produced increases in venous effluent lipoprotein lipase activity (the enzyme responsible for hydrolysis of triglycerides to free fatty acids). Bone marrow also stimulated the production of thromboxane B2 but not 6-ketoprostaglandin F1 alpha in the perfused lung. Both meclofenamate (1 microM), a cyclooxygenase inhibitor, and U-60,257 (10 microM), a lipoxygenase inhibitor, attenuated the bone marrow-induced pulmonary hemodynamic response, whereas only U-60,257 attenuated the increases in lung wet weight and the capillary filtration coefficient. In conclusion, pulmonary embolization induced by bone marrow results in increases in lung weight and the capillary filtration coefficient in the isolated Ringer-perfused rabbit lung. Pulmonary vasoconstriction is partially dependent on arachidonic acid metabolites but appears to be independent of circulating blood-formed elements. The lipid component of bone marrow or products derived from this component (e.g., free fatty acids and lipoxygenase products) may mediate the bone marrow-induced pulmonary edema.     

Effects of locally formed angiotensin II on renal hemodynamics

The kidney produces angiotensin II (AngII) by conversion of both locally formed and systemically delivered angiotensin I (AngI). The latter may be physiologically significant because the kidney can convert 20-25% of systemically delivered AngI. To determine possible differences between the effects of circulating and locally converted AngII, we compared the renal responses to renal arterial infusions of AngI and AngII in equiconstrictor doses. Both reduced the renal blood flow and increased the filtration fraction; it is important that the AngI infusions consistently reduced glomerular filtration rates (GFR), which indicates effects proximal to or at the glomerulus. Micropuncture experiments revealed that AngI infusions reduced proximal tubular and peritubular capillary pressures and the single-nephron GFR; glomerular capillary pressure was not altered significantly. AngI infusions increased both pre- and postglomerular resistances and reduced the glomerular filtration coefficient. In other studies designed to estimate net intrarenal AngII generation, it was determined that the kidney degrades about 90% of arterially delivered AngII. Thus, most of the AngII in renal venous blood was formed intrarenally. Local production of AngII was enhanced, in association with increased renin release, after reductions in renal arterial pressure. Such increases in intrarenal AngII production may contribute to the AngII-dependent changes in renal vascular resistance that occur in conditions where the renin-angiotensin system is stimulated.     

Sex-related effects on venous compliance and capillary filtration in the lower limb

Recent studies in humans have suggested sex differences in venous compliance of the lower limb, with lower compliance in women. Capillary fluid filtration could, however, be a confounder in the evaluation of venous compliance. The venous capacitance and capillary filtration response in the calves of 12 women (23.2 +/- 0.5 years) and 16 men (22.9 +/- 0.5 years) were studied during 8 min lower body negative pressure (LBNP) of 11, 22, and 44 mmHg. Calf venous compliance is dependent on pressure and was determined using the first derivative of a quadratic regression equation that described the capacitance-pressure relationship [compliance = beta1 + (2 x beta2 x transmural pressure)]. We found a lower venous compliance in women at low transmural pressures, and the venous capacitance in men was increased (P < 0.05). However, the difference in compliance between sexes was reduced and not seen at higher transmural pressures. Net capillary fluid filtration and capillary filtration coefficient (CFC) were greater in women than in men during LBNP (P < 0.05). Furthermore, calf volume increase (capacitance response + total capillary filtration) during LBNP was equivalent in both sexes. When total capillary filtration was not subtracted from the calf capacitance response in the calculation of venous compliance, the sex differences disappeared, emphasizing that venous compliance measurement should be corrected for the contribution of CFC.     

Decreased capillary filtration but maintained venous compliance in the lower limb of aging women

There are sex-related differences in venous compliance and capillary filtration in the lower limbs, which to some extent can explain the susceptibility to orthostatic intolerance in young women. With age, venous compliance and capacitance are reduced in men. This study was designed to evaluate age-related changes in venous compliance and capillary filtration in the lower limbs of healthy women. Included in this study were 22 young and 12 elderly women (23.1 +/- 0.4 and 66.4 +/- 1.4 yr). Lower body negative pressure (LBNP) of 11, 22, and 44 mmHg created defined transmural pressure gradients in the lower limbs. A plethysmographic technique was used on the calf to assess venous capacitance and net capillary filtration. Venous compliance was calculated with the aid of a quadratic regression equation. No age-related differences in venous compliance and capacitance were found. Net capillary filtration and capillary filtration coefficient (CFC) were lower in elderly women at a LBNP of 11 and 22 mmHg (0.0032 vs. 0.0044 and 0.0030 vs. 0.0041 ml.100 ml(-1).min(-1).mmHg(-1), P < 0.001). At higher transmural pressure (LBNP, 44 mmHg), CFC increased by approximately 1/3 (0.010 ml.100 ml(-1).min(-1).mmHg(-1)) in the elderly (P < 0.001) but remained unchanged in the young women. In conclusion, no age-related decrease in venous compliance and capacitance was seen in women. However, a decreased CFC was found with age, implying reduced capillary function. Increasing transmural pressure increased CFC in the elderly women, indicating an increased capillary susceptibility to transmural pressure load in dependent regions. These findings differ from earlier studies on age-related effects in men, indicating sex-specific vascular aging both in the venous section and microcirculation.     

Comparative characterization of reactions of skeletal muscle arterial and venous vessels to combined adrenergic effects

In experiments with the constant blood flow perfusion of the cat calf muscle and combined actions of adrenalin and noradrenaline were tested as to the blood flow resistance changes of the arterial and venous blood vessels. Separately applied the catecholamines evoked vascular resistance changes practically similar in value; combined effects of catecholamines realized in greater increase of arterial than venous resistance. In contrast to arterial vessels supramaximal stimuli resulted in much lesser constrictive effect as compared with reaction of intramural veins to separately applied catecholamines. Greater doses of catecholamines being combined, stability of effector system of skeletal muscle veins is decreased as compared to arteries.     

Evaluation of Starling forces in the equine digit

A pump-perfused extracorporeal digital preparation was used to evaluate blood flow, arterial pressure, venous pressure, isogravimetric capillary filtration coefficient, capillary pressure, and vascular compliance in six normal horses. From these data, pre- and postcapillary resistances and pre- and postcapillary resistance ratios were determined. Vascular and tissue oncotic pressures were estimated from plasma and lymph protein concentrations, respectively. By use of the collected and calculated data, tissue pressure in the digit was calculated using the Starling equation. In the isolated equine digit, isogravimetric capillary pressure averaged 36.7 mmHg, plasma and lymph oncotic pressures averaged aged 19.12 and 6.6 mmHg, respectively, interstitial fluid pressure averaged 25.6 mmHg, and the capillary filtration coefficient averaged 0.0013 ml.min-1.mm-1.100 g-1. Our results indicate that digital capillary pressure in the laterally recumbent horse is much higher than in analogous tissues in other species such as dog and human. However, the potential edemagenic effects of this high digital capillary pressure are opposed by at least two mechanisms: 1) a high tissue pressure and 2) a low microvascular surface area for fluid exchange and/or a low microvascular permeability to filtered fluid.     

Whole-body systemic transcapillary filtration rates, coefficients, and isogravimetric capillary pressures in Bufo marinus and Rana catesbeiana

Whole-body and organ-level transcapillary filtration rates and coefficients are virtually unexamined in ectothermal vertebrates. These filtration rates appear to be greater than in mammals when plasma volume shifts and lymphatic function are analyzed. Gravimetric techniques monitoring whole-body mass changes were used to estimate net systemic filtration in Bufo marinus and Rana catesbeiana while perfusing with low-protein Ringer's and manipulating venous pressure. Capillary pressures were estimated from arterial and venous pressures after measuring the venous to arterial resistance ratio of 0.23. The capillary filtration coefficient (CFC) for the two species was 25.2+/-1.47 mL min-1 kg-1 kPa-1. Isogravimetric capillary pressure (Pci), the pressure at which net fluid is neither filtered nor reabsorbed, was 1.12+/-0.054 kPa and was confirmed by an independent method. None of these variables showed a significant interspecific difference. The anuran CFC and Pci are significantly higher than those found using the same method on rats (7.6+/-2.04 mL min-1 kg-1 kPa-1 and 0.3+/-0.37 kPa, respectively) and those commonly reported in mammals. Despite the high CFC, the high Pci predicts that little net filtration will occur at resting in vivo capillary pressures.     

Vascular flow capacity of hindlimb skeletal muscles in spontaneously hypertensive rats

Total and regional skeletal muscle flows (radiolabeled microspheres) were determined in isolated maximally vasodilated hindquarters of spontaneously hypertensive rats (SHR) and age-matched (11-12 mo) normotensive Wistar-Kyoto rats (WKY) to assess the vascular flow capacity of the skeletal muscle vascular beds. Vascular flow capacity was estimated by measuring total hindquarters and regional muscle blood flows (under conditions of maximal vasodilation with papaverine or papaverine plus isoproterenol) over a wide range of perfusion pressures in WKY and SHR. Capillary exchange capacity was estimated by determining the capillary filtration coefficient. Isogravimetric capillary pressures and segmental vascular resistances were determined in each hindquarter. Isogravimetric flows and capillary pressures were not different between WKY and SHR. However, total and precapillary vascular resistances were significantly elevated in SHR, and postcapillary resistances were not different compared with WKY. Maximal capillary filtration coefficient values for the SHR group averaged 20% lower than WKY values, suggesting that hypertension was associated with a reduction in the microvascular surface area available for fluid exchange and, therefore, the capillary exchange capacity. Over the perfusion pressures studied, total hindquarters flows averaged 60% lower in SHR than in WKY. Flows to individual skeletal muscles averaged 76% lower in SHR than in WKY regardless of the muscle fiber type. Thus, modifications exist in the hindlimb skeletal muscle vasculature of SHR that reduces the capillary exchange capacity and limit the capacity of deliver flow at a given perfusion pressure gradient.     

Decrease in the effectiveness of a hypoxic stimulus during cooling of the vascular bed of an organ

Acute experiments on cats using perfusion of the innervated calf muscle and small intestinal vessels with self blood at a constant blood flow rate have established decreased sensitivity of vessels (cooled to 30 degrees C) to hypoxic stimulus effect (inhalation of 10% O2 in N2). The essence of the phenomenon consists in considerably smaller deviations of pre- and postcapillary resistance, capillary filtration coefficient, mean capillary pressure during simultaneous exposure to cold and hypoxia than during separate application of hypoxic or hypothermic stimuli. Organ distinctions in the degree and direction of changes in vascular resistance and metabolism have been observed.     

Defense reaction alters the response to blood loss in the conscious rabbit

The interaction of sensory stressors with the cardiovascular response to blood loss has not been studied. The cardiovascular response to a stressor (i.e., the defense reaction) includes increased skeletal muscle blood flow and perhaps a reduction in arterial baroreflex function. Arterial pressure maintenance during blood loss requires baroreflex-mediated skeletal muscle vasoconstriction. Therefore, we hypothesized that the defense reaction would limit arterial pressure maintenance during blood loss. Male, New Zealand White rabbits were chronically prepared with arterial and venous catheters and Doppler flow probes. We removed venous blood in conscious rabbits until mean arterial pressure decreased to <40 mmHg. We repeated the experiment with (air) and without (sham) simultaneous exposure to an air jet stressor. Air resulted in a defense reaction (e.g., mean arterial pressure = 94 +/- 1 and 67 +/- 1 mmHg for air and sham, respectively). Contrary to our hypothesis, air increased the blood loss necessary to produce hypotension (19.3 +/- 0.2 vs. 16.9 +/- 0.2 ml/kg for sham). Air did not reduce skeletal muscle vasoconstriction during normotensive hemorrhage. However, air did enhance renal vasoconstriction (97 +/- 3 and 59 +/- 3% of baseline for sham and air, respectively) during the normotensive phase. Thus the defense reaction did not limit but rather extended defense of arterial pressure during hemorrhage.     

Diameter changes in skeletal muscle venules during arterial pressure reduction

Previous studies in skeletal muscle have shown a substantial (>100%) increase in venous vascular resistance with arterial pressure reduction to 40 mmHg, but a microcirculatory study showed no significant venular diameter changes in the horizontal direction during this procedure. To examine the possibility of venular collapse in the vertical direction, a microscope was placed horizontally to view a vertically mounted rat spinotrapezius muscle preparation. We monitored the diameters of venules (mean diameter 73. 8 +/- 37.0 microm, range 13-185 microm) oriented horizontally and vertically with a video system during acute arterial pressure reduction by hemorrhage. Our analysis showed small but significant (P < 0.0001) diameter reductions of 1.0 +/- 2.5 microm and 1.8 +/- 3. 1 microm in horizontally and vertically oriented venules, respectively, upon reduction of arterial pressure from 115.0 +/- 26. 3 to 39.8 +/- 12.3 mmHg. The venular responses were not different after red blood cell aggregation was induced by Dextran 500 infusion. We conclude that diameter changes in venules over this range of arterial pressure reduction are isotropic and would likely increase venous resistance by <10%.     

Pulsatile pressure and flow in the skeletal muscle microcirculation

Although blood flow in the microcirculation of the rat skeletal muscle has negligible inertia forces with very low Reynolds number and Womersley parameter, time-dependent pressure and flow variations can be observed. Such phenomena include, for example, arterial flow overshoot following a step arterial pressure, a gradual arterial pressure reduction for a step flow, or hysteresis between pressure and flow when a pulsatile pressure is applied. Arterial and venous flows do not follow the same time course during such transients. A theoretical analysis is presented for these phenomena using a microvessel with distensible viscoelastic walls and purely viscous flow subject to time variant arterial pressures. The results indicate that the vessel distensibility plays an important role in such time-dependent microvascular flow and the effects are of central physiological importance during normal muscle perfusion. In-vivo whole organ pressure-flow data in the dilated rat gracilis muscle agree in the time course with the theoretical predictions. Hemodynamic impedances of the skeletal muscle microcirculation are investigated for small arterial and venous pressure amplitudes superimposed on an initial steady flow and pressure drop along the vessel.     

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.     

Venous occlusion measurement of pulmonary capillary pressure: effects of embolization

The effects of pulmonary arterial embolization on calculated pulmonary capillary pressure as determined by the venous occlusion technique are examined using a simple pressure-flow model for the lung. It is predicted that pulmonary, arterial embolization can induce significant underestimation of pulmonary capillary pressure in flowing vessels. This underestimation is related to the percent of vessels embolized and the caliber of pulmonary arteries that are embolized (i.e., the size of the emboli). Experimental verification of these theoretical findings is necessary before the conclusions can be extended to the interpretation of venous occlusion experiments in the lung.     

Enzymatic heterogeneity of the capillary bed of rat skeletal muscles

This study of the capillaries in rat skeletal muscle involved the use of a histochemical method that allows one to distinguish between arterial and venous portions of capillaries. Under controlled staining conditions, the arterial portion of the capillary bed reacts positively for alkaline phosphatase (AP) activity, and the venous portion is positive for dipeptidyl peptidase IV (DPP IV) activity. A short transitional capillary segment is positive for the activity of both enzymes. Capillaries of the normal soleus muscle and the red and white portions of the sternomastoid muscle have been quantitatively analyzed. Quantitative data demonstrated differences in capillary dimensions among the muscles studied. Capillaries of the white part of the sternomastoid were the longest, and they had the shortest DPP IV-positive segment (8% of the total capillary length). Capillaries of the soleus muscle were the shortest, and they also had short DPP IV-positive segments (16%). In contrast, the DPP IV-positive segments of the red part of the sternomastoid occupied 60% of the total capillary length. Survey cross sections reveal a mosaic distribution of patches of capillaries stained for AP and DPP IV activity. This study reveals that within given bundles of muscle fibers, the capillaries that run parallel to the muscle fibers are aligned relative to one another in such a manner that their arterial and venous segments are in register.     

Cellular localization of the endothelin receptor subtypes ET(A) and ET(B) in the rat heart and their differential expression in coronary arteries,veins, and capillaries

In the heart, the endothelin (ET)/endothelin-receptor system is markedly involved in pathophysiological mechanisms underlying various cardiac diseases. Based upon pharmacological studies both ET-receptor subtypes take part in the regulation of coronary vascular tone, however, their detailed cellular distribution in the coronary vascular bed based upon direct mRNA and protein detection is unknown. This issue was addressed in the rat heart by means of non-radioactive in situ hybridization, RT-PCR, and immunohistochemistry. Expression of vascular ET(A)-receptors was detected in arterial smooth muscle and capillary endothelium while ET(B)-receptors were present in arterial, venous, and capillary endothelium, and in arterial and venous smooth muscle cells. This differential distribution of the ET-receptor subtypes supports the concept that ET(A)- as well as ET(B)-receptors mediate arterial vasoconstriction, while postcapillary vascular resistance is exclusively regulated by ET(B)-receptors. The observed capillary endothelial expression of the ET(A)-receptor correlates with the known ability of ET(A)-receptor antagonists to attenuate increases in cardiac microvascular permeability during endotoxin shock and ischemia/reperfusion injury.