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V L Tucker

Publications and source records attributed to V L Tucker.

At least 19 recordsLinked to original sources
PubMed2001

Basal release of nitric oxide and its interaction with endothelin-1 on single vessel hydraulic permeability.

BACKGROUND: Both endothelin-1 (ET-1) and nitric oxide (NO) are released by the endothelium and are implicated in modulating the permeability of the endothelial barrier. The present study was designed to examine the interaction between ET-1 and NO and its influence on microvascular permeability as well as the role of NO in maintaining microvascular permeability. To isolate the direct effect of ET-1 and NO, experiments were conducted under conditions where hydraulic and oncotic pressures were controlled. METHODS: Postcapillary venules in the rat mesentery were perfused in situ and paired measurements of hydraulic permeability (Lp) obtained using the modified Landis micro-occlusion method. The effect of basal endogenous NO was tested by measuring the effects of perfusion with the NO synthase inhibitor Nw-nitro-L-arginine-methyl-ester (L-NAME) (100 micromol/L) on Lp (n = 6). In addition, Lp measured after a 15-minute perfusion with L-NAME (100 micromol/L) was compared with measures of Lp obtained after perfusion with a combined mixture of L-NAME (100 micromol/L) and ET-1 (80 pmol/L) (n = 6). RESULTS: Units for Lp are mean +/- SE x 10(-8) cm x sec(-1) x cm H2O(-1). Under basal conditions, in the absence of exogenous ET-1, NO synthase inhibition led to a significant increase in Lp from 5.7 +/- 0.5 to 9.8 +/- 1.4 (p = 0.02). Compared with L-NAME alone, ET-1 + L-NAME significantly decreased Lp from 10.3 +/- 0.8 to 5.7 +/- 0.6 (p = 0.006). CONCLUSION: Constitutive release of NO from the microvascular endothelium plays a role in maintaining a basal level of microvascular permeability. Decreases in microvascular permeability seen with the administration of ET-1 are not mediated via the release of NO. These findings suggest important roles for ET-1 and NO in maintaining and modulating microvascular permeability.

Animals↗
PubMed2000

Basal release of endothelin-1 and the influence of the ETB receptor on single vessel hydraulic permeability.

BACKGROUND: Endothelin-1 (ET-1) has a direct permeability decreasing effect on the microvasculature. The present study was designed to test the hypothesis that this effect is mediated via the endothelin B (ETB) receptor located on the microvascular endothelium and to determine whether basal microvascular permeability is dependent on constitutive release of ET-1. To isolate the direct effect of ET-1, experiments were conducted under conditions in which hydraulic and oncotic pressures were controlled. METHODS: Postcapillary venules in the rat mesentery were perfused in situ, and paired measurements of hydraulic permeability (Lp) were obtained using the modified Landis micro-occlusion method. Lp measured after a 15-minute perfusion with the ETB receptor blocker BQ-788 (1 micromol/L) was compared with measures of Lp obtained after perfusion with a combined mixture of BQ-788 and ET-1 (80 pmol/L) (n = 6). In addition, the effect of basal endogenous ET-1 was tested by measuring the effects of BQ-788 perfusion on Lp (n = 6). RESULTS: Units for Lp are mean +/- SE x 10(-8) cm x s(-1) cm H2O(-1). ETB receptor blockade prevented any decrease in Lp induced by ET-1 (BQ-788 alone = 7.9 +/- 0.7; BQ-788 + ET-1 = 8.2 +/- 0.8;p = 0.5). Under basal conditions and in the absence of exogenous ET-1, ETB receptor blockade led to a significant increase in Lp from 6.8 +/- 0.9 to 9.7 +/- 1.2 (p = 0.001). CONCLUSION: Decreases in microvascular permeability in single postcapillary venules after the administration of ET-1 are mediated via the ETB receptor. Constitutive release of ET-1 from the microvascular endothelium also plays a role in maintaining basal levels of permeability. These findings suggest important roles for ET-1 in maintaining and modulating microvascular permeability.

Animals↗
PubMed1999

Acute effects of tumor necrosis factor on hydraulic conductivity of mammalian postcapillary venules.

BACKGROUND: Tumor necrosis factor (TNF) is a cytokine that has been implicated in the development of capillary leak in sepsis. METHODS: We examined the direct effects of intraluminally applied TNF on microvessel hydraulic permeability (Lp) in the in situ mesentery of pentobarbital anesthetized female rats. Postcapillary venules were cannulated and perfused with Ringer's solution containing 0.5% albumin and washed erythrocytes. Transcapillary volume flow per unit surface area (Jv/S) was measured by using the modified Landis technique and Lp was calculated from the regression of Jv/S on pressures between 35 and 75 cm H2O. RESULTS: Under control conditions the Lp (mean +/- SE) was 1.06+/-0.08 x 10(-7) cm/(s x cm H2O) (n = 16). Lp was 0.87+/-0.12 x 10(-7) cm/(s x cm H2O) after a 20-minute perfusion with murine recombinant TNF at a concentration of 150 pg/mL (n = 5, p vs. control = 0.3). At a concentration of 10 ng/mL Lp was 1.15+/-0.15 x 10(-7) cm/(s x cm H2O) (n = 7,p vs. control = 0.6). In vessels perfused for 2 hours with TNF at 10 ng/mL, Lp was 0.96+/-0.33 x 10(-7) cm/(s x cm H2O) (n = 4, p = 0.66). At 100 ng/mL, Lp was 2.4+/-0.40 x 10(-7) cm/(s x cm H2O) (n = 7,p = 0.046). CONCLUSION: The acute intraluminal exposure to TNF, in the absence of other circulating factors, does not increase venular hydraulic permeability at concentrations of 150 pg/mL and 10 ng/mL. In vessels exposed at high or supraphysiologic concentrations (100 ng/mL), an acute twofold increase in Lp was demonstrated.

Analysis of Variance↗
PubMed1999

Direct actions of endothelin-1 on single vessel hydraulic permeability.

BACKGROUND: There is evidence that endothelin-1 (ET-1) increases extravasation of fluid and protein into vascular beds. The present study was designed to determine the direct effects of ET-1 on hydraulic permeability (Lp) when microvascular hydraulic and oncotic pressures are controlled. METHODS: Postcapillary venules in the rat mesentery were perfused in situ and paired measurements of Lp obtained by using the modified Landis micro-occlusion method. Lp measured after a 15-minute perfusion with Ringer's albumin solution (control) was compared with Lp after a subsequent 15-minute perfusion with one of three treatments: control (n = 4), 8 pM ET-1 (n = 6), or 80 pM ET-1 (n = 6). RESULTS: Baseline L for all vessels averaged (+/- SE) 8.1 +/-0.8 x 10(-8) cm x sec(-10 x cm H2O(-1) and was not significantly different between groups. Perfusion with either control or 8 pM ET-1 did not significantly change the Lp of any of the vessels. Significant decreases in Lp of 40 to 60% were observed in venules perfused with 80 pM ET-1. The average Lp in this group was 9.9 +/- 1.4 during baseline and decreased to 5.0 +/- 0.7 during ET-1 perfusion (p = 0.003). Washout of 80 pM ET-1 for periods of up to 15 minutes did not return Lp to baseline values. CONCLUSION: Low-dose ET-1 did not directly increase Lp in postcapillary venules. ET-1 at 80 pM, however, significantly decreased Lp. These data implicate factors other than a direct permeability-increasing effect in ET-1. At higher concentrations, ET-1 may have a protective effect on endothelial barrier function.

Analysis of Variance↗
PubMed1998

Measurement of microvascular transport parameters of macromolecules in tissues and organs of intact animals.

A critical analysis is presented of two widely used approaches to measurement of microvascular transport of large molecules in intact animals: (1) measurement of lymph flow and macromolecular solute concentration relative to plasma, and (2) tissue accumulation of tracer macromolecules. To demonstrate the advantages and limitations of each method, experimental results which permit direct comparison of the two methodologies are reviewed and analyzed, and sources of error in each pointed out. It is concluded that both approaches are valid under the appropriate conditions: steady state of lymph, initial transient state for tissue uptake. These conditions are mutually exclusive, but complementary. When the requirements for neither lymph collection or tissue accumulation alone can be satisfied experimentally, a combination of the two approaches can yield valid results.

Albumins↗
PubMed1997

Methods for studying microvascular barrier function in ischemia-reperfusion injury.

Ischemia-reperfusion (I/R) injury is accompanied by functional disturbances in the microcirculation that often translate into significant morbidity and mortality. We present an overview of methods to evaluate microvascular barrier properties and how these methods can be applied to the study of I/R injury. Included is a summary of techniques for measuring 1) fluid and macromolecule flux from the vascular compartment into the interstitial space of tissues and 2) the permeability parameters of microvascular wall. Several experimental models will be surveyed including whole animal, isolated organ, individually perfused microvessels and cultured endothelial cells using examples from our own studies and work of other investigators relating to I/R-induced endothelial injury. The strengths and weaknesses of these different approaches are discussed.

Animals↗
PubMed1997

Atrial natriuretic peptide levels and plasma volume contraction in acute alveolar hypoxia.

Arterial oxygen tensions (PaO2), atrial natriuretic peptide (ANP) concentrations, and circulating plasma volumes (PV) were measured in anesthetized rats ventilated with room air or 15, 10, or 8% O2 (n = 5-7). After 10 min of ventilation, PaO2 values were 80 +/- 3, 46 +/- 1, 32 +/- 1, and 35 +/- 1 Torr and plasma immunoreactive ANP (irANP) levels were 211 +/- 29, 229 +/- 28, 911 +/- 205, and 4,374 +/- 961 pg/ml, respectively. At PaO2 < or = 40 Torr, irANP responses were more closely related to inspired O2 (P = 0.014) than to PaO2 (P = 0.168). PV was 36.3 +/- 0.5 microliters/g in controls but 8.5 and 9.9% lower (P < or = 0.05) for 10 and 8% O2, respectively. Proportional increases in hematocrit were observed in animals with reduced PV; however, plasma protein concentrations were not different from control. Between 10 and 50 min of hypoxia, small increases (+40%) in irANP occurred in 15% O2; however, there was no further change in PV, hematocrit, plasma protein, or irANP levels in the lower O2 groups. Urine output tended to fall during hypoxia but was not significantly different among groups. These findings are compatible with a role for ANP in mediating PV contraction during acute alveolar hypoxia.

Animals↗
PubMed1997

Acute alveolar hypoxia increases blood-to-tissue albumin transport: role of atrial natriuretic peptide.

Plasma immunoreactive atrial natriuretic peptide (irANP) and blood-to-tissue clearance of 131I-labeled rat serum albumin (CRSA) were examined in anesthetized rats during hypoxic ventilation (n = 5-7/group). Hypoxia (10 min) increased irANP from 211 +/- 29 (room air) to 229 +/- 28 (15% O2, not significant), 911 +/- 205 (10% O2), and 4,374 +/- 961 pg/ml (8% O2), respectively. Graded increases in CRSA were significant at 8% O2 in fat (3.6-fold), ileum (2.2-fold), abdominal muscles (2.0-fold), kidney (1.8-fold), and jejunum (1.4-fold). CRSA was decreased in back skin and testes; heart, brain, and lungs were unaffected. The increases in CRSA were related to irANP and not to arterial PO2. Circulating plasma volume was negatively correlated with whole body CRSA. Graded increases in extravascular water content (EVW) were found in the kidney, left heart, and cerebrum and were positively related to CRSA in the kidney. EVW decreased in gastrointestinal tissues; the magnitude was inversely related to CRSA. We conclude that ANP-induced protein extravasation contributes to plasma volume contraction during acute hypoxia.

Albumins↗
PubMed1996

Plasma ANP levels and protein extravasation during graded expansion with equilibrated whole blood.

The relationship between plasma immunoreactive atrial natriuretic peptide (irANP) and radiolabeled albumin clearance (CBSA) in multiple tissues after graded volume stimuli was examined. To obtain a pure volume stimulus, pentobarbital sodium-anesthetized rats (5 or 6 per group) were equilibrated with a reservoir of blood by a femoral arteriovenous shunt, and volume expansion (VE) was produced by adjusting reservoir outflow. Peak increases in central venous pressure (CVP) during VE equal to 2 and 4% of the body weight over 5 min were 3.6 +/- 0.2 and 7.0 +/- 0.3 mmHg, and plasma irANP levels measured at 40 min post-VE were elevated 1.9- and 4.1-fold above baseline, respectively. Graded increases in CBSA measured between 5 and 35 min post-VE occurred in selective tissues, including intestine, visceral fat, lung, and muscle (P < or = 0.05). In separate animals, the level of VE was maintained after 2% VE by slower administration of an additional 2% VE for the remaining 30 min. This resulted in a more sustained CVP elevation and larger increases in irANP levels and CBSA compared with either 2 or 4% VE. Furthermore, equations derived from previous work in this laboratory involving intravenous administration of ANP predicted the magnitude of CBSA elevation during maintained VE. These findings support a role for ANP in regulating transcapillary protein distribution during acute intravascular expansion.

Animals↗
PubMed1996

Contribution of ANP to plasma protein escape during VE: effects of thiorphan and atrial appendectomy.

The effects of endopeptidase inhibition and right atrial appendectomy (AA) on plasma immunoreactive atrial natriuretic peptide (irANP) concentrations and extravascular accumulation of 131I-labeled bovine serum albumin (CBSA) during volume expansion (VE) were examined in pentobarbital sodium-anesthetized rats (n = 5 per group). Compared with controls, infusion of isoncotic albumin (30 ml/kg) increased central venous pressure (CVP) by 5.5 mmHg, plasma irANP by 7-fold, and CBSA in multiple tissues by 1.6- to 4-fold (P < or = 0.05). Inhibition of ANP metabolism with thiorphan (40 mg/kg) had no effect in control animals but increased plasma irANP (+118%) and CBSA (+30-100%) compared with VE alone (P < or = 0.05). Likewise, interference with ANP release by AA reduced plasma irANP (-80%) and CBSA (-30 to -80%) response to VE in parallel (P < or = 0.05). The peak increase in CVP during VE was not affected by either of these manipulations. It is concluded that endogenous ANP increases plasma protein extravasation independent of volume and pressure disturbances during acute intravascular expansion.

Animals↗
PubMed1995

Blood-to-tissue albumin transport in rats subjected to acute hemorrhage and resuscitation.

Hemorrhage induces a rapid redistribution of protein from extravascular spaces into the blood. We studied the effects of acute, nontraumatic hemorrhage on tracer-albumin clearances into individual tissues of rats to determine if reduced protein extravasation could account for intravascular protein gain. Three groups were studied: 1) HEM animals were anesthetized with pentobarbital sodium and bled to a mean arterial pressure of 50 mmHg for 90 min; 2) HEM-RS animals were treated identical to group 1 and then resuscitated with 5% bovine serum albumin (BSA) until baseline arterial pressures were regained; 3) SHAM animals served as time controls. Hemodynamic variables were measured periodically throughout hemorrhage and clearance periods, and plasma samples were collected prior to death for protein and hormone analysis. Plasma clearance of 131I-BSA into individual tissues was measured over the final 30 min of each protocol with a terminal injection of 125I-BSA used to correct for intravascular volume. Reduction of blood volume by 35% in HEM-treated animals resulted in a marked decrease in albumin transport relative to the SHAM group (p < or = .05) in the following tissues: skeletal muscle (-65%), skin (-49%), ileum (-75%), cecum (-66%), colon (-67%), heart (-67%), and lung (-71%). Significant changes were not observed in the remaining tissues sampled: pancreas, kidney, and cerebrum. Albumin clearances in the HEM-RS group were slightly but not significantly lower than SHAM animals except for skeletal muscle, where transport remained depressed following resuscitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Blood-tissue transport of exogenous albumin and immunoglobulin G in genetically analbuminemic rats.

Tracer uptake studies were carried out in adult female Nagase (NA) strain analbuminemic rats [derived from Sprague-Dawley (SD) stock] and in adult female SD controls to determine the extent to which capillary permeability to plasma proteins is altered in the absence of endogenous albumin. Accessory measurements (arterial pressure, central venous pressure, plasma and interstitial fluid protein concentrations and oncotic pressures, plasma volume, and interstitial fluid volume) confirm the report of Joles et al. [Am. J. Physiol. 257 (Renal Fluid Electrolyte Physiol. 26): F23-F28, 1989] that shows elevated plasma volumes, normal interstitial fluid volumes, nearly normal plasma oncotic pressures (due to elevated globulin concentrations), and lower interstitial fluid oncotic pressures. In skin, skeletal muscles, and heart muscle, clearances of exogenous heterologous (bovine) albumin were 20-40% higher in NA than in SD controls. In intestine, albumin clearances were 20-30% lower. In NA rats blood-to-tissue clearances of heterologous (bovine) immunoglobulin G in skin and heart were higher and in the intestine they were lower than in SD controls; however, clearances in skeletal muscles were not elevated. The differences between NA and SD are small compared with the large increases in macromolecular permeabilities reported by others for organs and single microvessels perfused with albumin-free fluids.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1992

Tissue-specific effects of physiological ANP infusion on blood-tissue albumin transport.

Blood-tissue transport of 131I-labeled bovine serum albumin (BSA) during intravenous infusion of synthetic atrial natriuretic peptide (ANP) was examined in anesthetized male Wistar rats. Plasma volumes were maintained at pre-ANP levels by infusion of 2% BSA in lactated Ringer solution (LR) to minimize compensatory responses to ANP-induced hypovolemia. 131I-BSA clearance was measured over 30 min, and 125I-BSA was injected terminally to correct for intravascular volume. Thirty-minute infusion of 20 ng.kg-1.min-1 ANP resulted in a tissue-selective increase in 131I-BSA clearance in jejunum and colon compared with controls given LR only. Smaller but significant increases in tracer clearance also were observed in fat, kidney, left ventricle, and skeletal muscle exposed to 400 ng.kg-1.min-1 ANP. The observed elevation in tracer albumin extravasation was not associated with any measurable increase in tissue extravascular water content. Furthermore, it was shown that coupling of 131I-BSA transport to filtration induced by hindlimb venous congestion was similar in control and ANP-treated rats. In a second series of experiments, plasma ANP levels were determined after 30-min ANP infusions from 0 to 180 ng.kg-1.min-1. Significant linear associations between physiological ANP levels (62-578 pg/ml) and 131I-BSA clearance were demonstrable for small intestine, colon, fat, kidney, and skeletal muscle but not for skin, heart, diaphragm, and lung. We conclude that raising plasma ANP by infusion of the synthetic peptide results in a filtration-independent, tissue-selective increase in albumin transport. Tissue uptake of albumin is a potential mechanism for extrarenal fluid shift during circulatory volume overload.

Animals↗
PubMed1991

AIDS and adolescents. How can you help them reduce their risk?

AIDS in adolescents (0.4% of all cases) is a problem of increasing importance in the United States. Infection with the human immunodeficiency virus (HIV) exists in high schools and on university campuses, and it presents a real and immediate threat to teenaged Americans who engage in drug abuse and sexual activity. Appropriately targeted educational efforts are needed to limit HIV transmission among adolescents. Most adolescents are aware of the high-risk activities that may lead to HIV transmission. However, only about one third alter their sexual behavior to avoid AIDS. It is important to move beyond imparting knowledge about AIDS transmission and to move toward changing risky behavior. Strategies for AIDS risk reduction in adolescents should be implemented now across the country. Appropriate support and intervention are urgently needed for adolescents at high risk.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Evidence for cholinergic regulation of microvessel hydraulic conductance during tissue hypoxia.

Cholinergic regulation of single-vessel hydraulic conductivity (Lp) during normoxia and hypoxia was tested in single mesenteric vessels of pithed frogs (Rana pipiens). Capillaries were cannulated in situ and perfused with frog Ringer's solution containing 10 mg/ml albumin and human erythrocytes while the mesentery was continuously superfused with frog Ringer's solution (15 degrees C). Lp was first measured under normoxic (room air equilibrated) conditions by the modified Landis microocclusion method. Repeated measurements of filtration coefficient under control conditions, for periods up to 80 minutes, demonstrated that Lp did not change with time in normoxic vessels (n = 18). After initial control measurement (Lpo), perfusion with 1 microM acetylcholine increased Lp by 4.6 +/- 1.0-fold (mean +/- SEM, n = 6). The response to acetylcholine was antagonized by the addition of 10 microns atropine to the perfusate (Lp/Lpo = 1.8 +/- 0.4). Perfusion with atropine alone reduced Lp in three of six capillaries Lp/Lpo = 0.56 +/- 0.04); Lp in the remaining three vessels was unaffected. Tissue hypoxia was simulated by exposing the mesentery to deoxygenated superfusate Po2 less than or equal to 10 mm Hg) for 10-15 minutes. Tissue hypoxia had no effect on Lp in atropine-treated vessels (n = 8). Without atropine, tissue hypoxia increased Lp by 2.3 +/- 0.7-fold, whereas the addition of atropine completely antagonized this response (n = 5). In contrast to the inhibitory action of atropine during tissue hypoxia, Lp rose 5.2 +/- 1.6-fold (n = 4) in vessels simultaneously exposed to deoxygenated perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1988

O2 modulation of single-vessel hydraulic conductance.

To investigate the response of the microvascular endothelial barrier to O2 lack, hydraulic conductivities (Lp) were compared under control and hypoxic conditions. In 29 decerebrate frogs (Rana pipiens) the mesentery was exposed and continuously superfused with room air-equilibrated frog Ringer (14 degrees C, pH 7.4). Single mesenteric microvessels (15- to 50-microm diam) were cannulated and perfused with frog Ringer containing 5-40 mg/ml bovine serum albumin and 5-10% (vol/vol) human erythrocytes. The modified Landis technique was used to measure transmural water flux per unit area (Jv/S) from marker red cell movement at pressures ranging from 15 to 45 cmH2O. In 21 vessels, a 10-min superfusion with 100% N2-equilibrated Ringer increased Lp 2.4-fold (+/- 0.72 SD) over control (P less than or equal to 0.05). In an additional six vessels, simultaneous exposure to 100% N2-equilibrated perfusate and superfusate resulted in a 10-fold (+/- 3.0) increase in Lp (P less than or equal to 0.05). In 15 of the vessels, a 10- to 75-min reexposure to control conditions decreased Lp, averaging a 77% recovery toward base line. These data support an active role for O2 in the regulation of microvascular membrane permeability, which appears to be sensitive to the severity of O2 lack. The rapid increase in capillary water conductivity following exposure to hypoxic conditions may be the initial process in the events leading to edema formation.

Animals↗
PubMed1987

Increased capillary hydraulic conductivity induced by atrial natriuretic peptide.

The small molecular weight peptide, atrial natriuretic peptide (ANP), produces marked sodium and water excretion. The peptide, extracted from several species of vertebrate heart, also has been shown to increase glomerular filtration and reduce plasma volume. Several mechanisms have been proposed to account for the action of the peptide but remain undefined. In the present report, the ANP-induced alterations in transcapillary water movement were directly assessed. The modified Landis technique was used to measure single capillary hydraulic conductivity (Lp) of vessels from the frog mesenteric circulation. In 6 individual microvessels, Lp was measured under control conditions and again during perfusion with 10 X 10(-6) M ANP. The Lp increased in each vessel by a mean of 3.79-fold (+/- 2.09 SD). In 4 of these vessels, an additional measurement of Lp was repeated under control conditions; the capillary filtration coefficient returned to control levels. It was concluded that ANP directly and reversibly elevates capillary hydraulic conductivity; this response is independent of changes in capillary hydrostatic pressure or surface area.

Animals↗