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J N Benoit

Publications and source records attributed to J N Benoit.

At least 37 records · Page 2Linked to original sources
PubMed1993

Microvascular pressure and albumin extravasation after leukocyte activation in hamster cheek pouch.

The effects of leukotriene B4 (LTB4) and N-formyl-methionyl-leucylphenylalanine (FMLP) on transmicrovascular exchange of fluorescein isothiocyanate (FITC)-labeled serum albumin and dextran (molecular mass, 150,000 Da) were evaluated in hamster cheek pouch utilizing measurements of microvascular pressure and global efflux of the macromolecular markers into the tissue suffusate. Exposure of the suffused pouch to 1.0 microM LTB4 failed to alter microvascular pressure from its control level. The microvascular clearance of FITC-albumin rose to a peak value of 1.7 times the control value at a LTB4 concentration of 1.0 microM; the rate of albumin extravasation did not change from the normal level at a concentration of 0.1 microM. The extravasation rate of FITC-dextran was elevated with both doses of LTB4; the leukocyte chemotactic agent elicited 2.4- and 9.7-fold increments in peak clearance of dextran at concentrations of 0.1 and 1.0 microM, respectively. FMLP elicited a twofold increase in venular and terminal arteriolar pressures at a concentration of 1 microM; at the same concentration, the albumin clearance rose 3.5-fold. The results suggest that albumin transport remains near the normal level after LTB4 elicits massive migration of leukocytes across the venular membrane. By contrast, albumin transport is greatly accelerated following exposure to the chemotactic peptide FMLP; ultrastructural and physiological evidence suggests that the leakage of albumin is augmented by increases in microvascular permeability and filtration pressure. The results also reinforce previous ultrastructural observations from our laboratory indicating that diapedesis per se is not a cause of microvascular hyperpermeability in inflammatory reactions.

Animals↗
PubMed1993

Capillary filtration during acute inflammation: role of adherent neutrophils.

Fluid filtration rate with respect to surface area (Jv/S) was measured in capillaries of rat mesentery by a micro-occlusion technique. Superfusion of the mesentery with 100 nM platelet-activating factor (PAF) caused a fivefold increase in Jv/S (control, mean +/- SE = 0.016 +/- 0.002 micron/s, n = 44 rats; PAF, 0.078 +/- 0.010, n = 10), whereas 20 nM leukotriene B4 (LTB4) had no effect (0.010 +/- 0.003, n = 8). These doses of PAF and LTB4 induced a similar level of leukocyte adherence to venular endothelium. Neutrophils play a role in PAF-mediated increases in Jv/S, since a significantly lower Jv/S was elicited by PAF superfusion in neutropenic rats (0.024 +/- 0.006, n = 7). Monoclonal antibodies (MAb) directed against either the leukocyte adhesion glycoprotein CD11/CD18 (0.037 +/- 0.006, n = 8) or the endothelial cell adhesion molecule P-selectin (0.025 +/- 0.004, n = 8) also attenuated PAF-induced capillary filtration, whereas a nonbinding form of the P-selection MAb had no inhibitory effect (0.066 +/- 0.024, n = 3). These results indicate that PAF, but not LTB4, enhances capillary fluid filtration rate. While neutrophils do not adhere to endothelium in capillaries exposed to PAF, they do appear to contribute significantly to the PAF-induced capillary fluid filtration.

Animals↗
PubMed1992

Hepatic oxidant and antioxidant systems in portacaval-shunted rats.

The purpose of the present study was to determine the effects of chronic portal diversion on antioxidant levels in the rat liver. Male Sprague-Dawley rats (n = 32) were used for these studies. An end-to-side portacaval anastomosis was constructed in 17 of the rats. Sham-operated rats (n = 15) served as controls. Two weeks later, hepatic blood flow was measured by the radioactive microsphere technique and the liver was harvested for biochemical measurement of catalase, manganese superoxide dismutase, copper-zinc superoxide dismutase, selenium glutathione peroxidase, xanthine oxidase, xanthine dehydrogenase and reduced glutathione (acid soluble sulfhydryls). Total hepatic blood flow was approx. 40% lower in portacaval-shunted rats when compared to sham-operated control rats. Total superoxide dismutase (SOD) and xanthine dehydrogenase (XD) levels were significantly reduced in the liver of shunted rats when compared to controls. Xanthine oxidase activity was unaltered. The decreased superoxide dismutase levels were exclusively due to reductions in the cytosolic Ca/Zn SOD; Mn SOD levels were unaltered. These data are consistent with oxidant stress and suggest that the liver of subjects with conditions characterized by decreased portal blood flow may be more susceptible to oxidant-induced liver injury.

Animals↗
PubMed1992

Effects of f-Met-Leu-Phe-induced inflammation on intestinal lymph flow and lymphatic pump behavior.

Previous studies in the literature indicate that intraenteric placement of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe) evokes an intestinal inflammatory response characterized by an accumulation of interstitial fluid and increased lymph flow. Furthermore, it is known that movement of lymph away from the intestine is dependent on the rhythmic pumping of lymph by collecting lymphatics in the mesentery. The purpose of the present study was to determine whether the f-Met-Leu-Phe-induced increase in lymph formation is countered by an increase in lymphatic pump efficiency. Male Sprague-Dawley rats were anesthetized, and a segment of ileum with adjacent mesentery was exteriorized. The mesentery was positioned over an optical window, and a 100-microns collecting lymphatic was selected for study. The preparation was transferred to a video microscope, and the activity of the lymphatic pump was monitored under control conditions and during intraluminal infusion of 1 microM f-Met-Leu-Phe. Lymph propulsion by the lymphatic pump was calculated from the product of stroke volume and contraction frequency. In one group of animals, total lymph flow was determined by cannulating the lymphatic draining the ileal segment. Total lymph flow increased following f-Met-Leu-Phe placement in the intestine. The increased lymph flow was paralleled by a rise in lymphatic pumping. The rise in lymph propulsion by the lymphatic pump resulted exclusively from an increased stroke volume, inasmuch as contraction frequency did not change. The results of the present study suggest that activation of the lymphatic pump during acute inflammation may be important in preventing interstitial edema.

Animals↗
PubMed1991

Role of bile acids in splanchnic hemodynamic response to chronic portal hypertension.

Previous studies from our laboratory suggest that humoral factors, namely glucagon, can account for approximately 30% of the splanchnic vasodilation in rats with prehepatic portal hypertension. A reduced vascular sensitivity to norepinephrine, vasopressin, and angiotensin II may contribute to the splanchnic vasodilation. However, neither glucagon nor an altered vasoconstrictor sensitivity can fully account for the splanchnic vasodilation observed in portal hypertensive subjects. Therefore, the present study was designed to examine the role of bile acids in the splanchnic hyperemia of portal hypertension since (1) serum bile acids are elevated in portal hypertensive subjects and (2) bile acids are potent intestinal vasodilators. Prehepatic portal hypertension was induced in Sprague-Dawley rats by surgical constriction of the portal vein. Ten to 14 days after the induction of portal hypertension, the enterohepatic circulation of control and portal hypertensive rats was surgically interrupted. The animals were placed in Bollman restraint cages and allowed to recover. Eighteen to 24 hr later, the rats were anesthetized with sodium pentobarbital and regional blood flow measured with radiolabeled microspheres. Normal and portal hypertensive animals without bile fistula served as controls. Plasma bile acid levels measured by radioimmunoassay were approximately 3.8 times higher in portal hypertensive animals than in control. Bile duct cannulation effectively depleted both normal and portal hypertensive animals of their circulating bile acid pool and significantly reduced portal venous inflow in portal hypertensive but not in control rats. A role for bile acids as partial mediators of the splanchnic hyperemia of portal hypertension is suggested since bile acid depletion did not completely abolish the gastrointestinal hyperemia.

Animals↗
PubMed1991

Intestinal vascular sensitivity to vasopressin in portal hypertensive rats.

The intestinal vascular responsiveness to arginine vasopressin was evaluated in rats with chronic portal hypertension. Male Sprague-Dawley rats were made portal hypertensive by stenosis of the portal vein. Ten to twelve days after the induction of chronic portal hypertension, the responsiveness of the small intestinal circulation to cumulative doses of vasopressin was evaluated using an isolated pump-perfused small intestinal preparation. The ED50 for maximal vasoconstriction was increased twofold in portal hypertensive rats compared with control rats. To determine if the impaired responsiveness to arginine vasopressin was related to the hyperglucagonemia of chronic portal hypertension, plasma glucagon levels were elevated in normal rats to levels previously measured in portal hypertensive rats (i.e. approximately 450 pg/mL), and the dose response studies were repeated. Glucagon significantly attenuated the responsiveness of the intestinal vasculature to vasopressin. Equipotent doses of nitroprusside also attenuated intestinal vascular responsiveness to vasopressin. The results indicate that there is a reduced vascular sensitivity to vasopressin in the intestine of portal hypertensive animals and suggest that elevations in circulating vasodilators in portal hypertensive conditions may partially explain this altered vascular responsiveness.

Animals↗
PubMed1991

Intestinal microvascular responsiveness to norepinephrine in chronic portal hypertension.

Effects of chronic prehepatic portal hypertension on intestinal microvascular sensitivity to norepinephrine (NE) were studied. Normal and portal hypertensive rats were anesthetized, and the intestine was prepared for in vivo microscopic observation. The preparation was transferred to a video microscope and a first-, second-, or third-order submucosal arteriole (i.e., 1A, 2A, or 3A, respectively) selected for study. Microvascular diameter and arteriolar erythrocyte velocity were measured on-line, and arteriolar blood flow was subsequently calculated as the product of velocity and vessel cross-sectional area. Once steady-state conditions were reached, the preparation was exposed to incremental doses of NE and microvessel responses were recorded. Cumulative log dose-response curves relating the change in arteriolar blood flow and vessel diameter to NE concentration were constructed for each group of arterioles and the ED50 for maximal response obtained from each dose-response relationship. NE ED50 for 1A blood flow was significantly higher in portal hypertensive rats (2.57 +/- 0.25 microM) compared with control rats (1.48 +/- 0.19 microM). Analysis of the diameter responses of 1A, 2A, and 3A indicated that the loss of vascular NE sensitivity in chronic portal hypertension was localized to the terminal submucosal arterioles (2A and 3A). No differences in the diameter response of 1A were observed between normal and portal hypertensive rats. Separate experiments were conducted to test if glucagon, a known mediator of the hyperdynamic intestinal circulation in portal hypertension, could acutely alter NE responsiveness in normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Relationships between lymphatic pump flow and total lymph flow in the small intestine.

Response of collecting lymphatics to acute elevations in lymph formation was studied in vivo. Mesentery of 33 rats was prepared for intravital microscopic study, and indexes of lymph propulsion (contraction frequency, stroke volume, and ejection fraction) were monitored. In 14 rats, total lymph flow was measured by cannulating the main intestinal lymph trunk. After a control period, lymph flow was increased by hemodilution with isotonic saline. Right atrial pressure did not significantly increase during the hemodilution period. Total lymph flow increased to approximately 25 times control. Lymph propulsion (the product of stroke volume and contraction frequency) decreased in five lymphangions (group I). In 22 lymphangions, lymph propulsion increased one to five times control (group II). The remaining six lymphangions increased lymph propulsion by greater than five times control (group III). Group I possessed the largest end-diastolic diameter, highest baseline contraction frequency, and did not dilate as lymphatic filling increased. Group III possessed the smallest initial end-diastolic diameter and lowest baseline contraction frequency, and end-diastolic diameter doubled as lymphatic filling increased. The characteristics of group II were between those of groups I and III. Total lymph flow and lymph propulsion by group III lymphangions tended to agree when lymph flow was less than five times control. In more edematous conditions, total lymph flow exceeded lymphatic pump flow. The characteristics of group II were between those of groups I and III. Analysis of the location of various sized lymphangions within the lymphatic network indicated that the smaller group III lymphangions were located nearer the intestinal wall, and the larger group I lymphangions were nearer the outflow from the mesentery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Leukocyte adherence to venular endothelium during ischemia-reperfusion.

Xanthine oxidase-derived oxidants and leukocytes have been implicated in the microvascular injury associated with reperfusion of ischemic intestine. The objective of this study was to determine whether xanthine oxidase-derived oxidants play a role in the leukocyte-microvascular interactions initiated by ischemia-reperfusion. Adherence and extravasation of leukocytes were monitored in cat mesenteric venules subjected to 1 h of ischemia (blood flow reduced to 20% of control) and reperfusion. Leukocyte rolling velocity, vessel diameter, and red cell velocity were also measured in control (untreated) animals and in animals pretreated with either allopurinol or superoxide dismutase. The responses of venular blood flow, wall shear rate, and leukocyte rolling velocity to ischemia and reperfusion did not differ between the three experimental groups. In control animals, 1 h of ischemia was associated with significant adherence and extravasation of leukocytes with reperfusion greatly enhancing these responses. Allopurinol treatment did not alter the responses to ischemia per se, yet it largely prevented the further increment in adherence and extravasation associated with reperfusion. Superoxide dismutase treatment attenuated the leukocyte responses elicited by both ischemia and reperfusion. Our observations that both allopurinol and superoxide dismutase attenuate reperfusion-induced leukocyte adherence and extravasation are consistent with the hypothesis that xanthine oxidase-derived oxidants initiate the leukocyte infiltration induced by reperfusion of ischemic intestine.

Allopurinol↗
PubMed1989

Dimethylsulfoxide prevents chemoattractant-induced leukocyte adherence.

The objective of this study was to determine whether dimethylsulfoxide (DMSO) influences chemoattractant-induced leukocyte adherence in the intestinal microcirculation. The distal colon of Sprague-Dawley rats was prepared for intravital microscopic observation of 25-35 microns diameter venules located in the muscularis externa. The number and average velocity of rolling leukocytes and the number of leukocytes adherent to the venular endothelial surface were determined from recorded video images. After a control period of observation, either N-formyl-methionyl-leucyl-phenylalanine (FMLP) or leukotriene B4 (LTB4) was added to the serosal superfusion solution. Both FMLP (1 microM) and LTB4 (1 microM) consistently caused leukocytes to adhere to venular endothelium. DMSO, at concentrations ranging between 2.5 and 140 mM, inhibited FMLP-induced leukocyte adherence in a dose-related manner. LTB4-induced leukocyte adherence was also significantly attenuated by DMSO. Leukocyte rolling velocity and leukocyte flux were not affected by DMSO. These results indicate that DMSO significantly inhibits leukocyte adherence at concentrations commonly used for its hydroxyl radical scavenging properties.

Animals↗
PubMed1989

Characterization of intact mesenteric lymphatic pump and its responsiveness to acute edemagenic stress.

The contractile properties of the mesenteric collecting lymphatics of the rat were analyzed under control conditions and during periods of enhanced lymph formation using in vivo microscopic techniques. Pressure and diameter were simultaneously monitored in microscopic collecting lymphatics, and lymphatic pump function was analyzed in accordance with basic principles of cardiac mechanics. The lymphatic contractile cycle was divided into two phases of systole and four phases of diastole. Under control conditions, lymphatics contracted with a frequency of 6.4 +/- 0.61 beats/min and ejected approximately 67% of their end-diastolic volume. Ten minutes after the rate of lymph formation was elevated by plasma dilution, end-diastolic diameter, contraction frequency, ejection fraction, and stroke volume increased. Pressure in the lymphatic network became less pulsatile in high lymph flow states. Contractility, an index of inotropic changes in lymphatic pump, was unaltered when lymph flow was increased by plasma dilution. Furthermore, the maximal shortening velocity of lymphatic smooth muscle did not change during periods of enhanced lymph flow. Thus it appears that passive increases in the rate of lymph formation exert few, if any, inotropic effects on the lymphatic pump. The augmented stroke volume and contraction frequency appear to result mainly from intrinsic stretch-dependent mechanisms set in motion by elevated preload. These data represent the first comprehensive characterization of both the flow-generating and muscle characteristics of intact collecting lymphatics and provide a basis for future studies on the physiological regulation of lymphatic contraction.

Animals↗
PubMed1988

Intestinal microvascular adaptation to chronic portal hypertension in the rat.

Microvascular pressures, diameters, and flow velocities were measured in the small intestine of rats with chronic stenosis of the portal vein. Ten days after portal vein stenosis, portal venous pressure increased (13.8 +/- 0.4 mmHg vs, 7.3 +/- 0.5 mmHg; p less than 0.05) whereas systemic arterial pressure decreased (94.2 +/- 2.0 mmHg vs. 106.5 +/- 1.6 mmHg; p less than 0.05). Red blood cell centerline velocity, measured in first-order arterioles, was significantly higher in portal hypertensive rats (24.3 +/- 1.2 mm/s vs. 19.6 +/- 1.3 mm/s), yet there was no significant change in the diameters of these vessels. Microvascular pressures and diameters of first- and second-order arterioles were not different between control and portal hypertensive rats. However, both pressure (34.3 +/- 2.7 mmHg vs. 28.0 +/- 1.8 mmHg) and diameter (30.4 +/- 0.6 microns vs. 21.4 +/- 2.1 microns) were significantly increased in the third-order arterioles of portal hypertensive rats. A consistent elevation in pressure was observed throughout the distal segments (capillaries to first-order venules) of the intestinal microcirculation of portal hypertensive rats. The results of these studies indicate that the increased intestinal vascular pressures associated with chronic portal hypertension result from a combination of reduced arteriolar resistance and venous congestion.

Adaptation, Physiological↗
PubMed1988

Role of glucagon in intestinal hyperemia associated with early experimental diabetes mellitus.

The role of glucagon as a blood-borne mediator of the intestinal hyperemia associated with experimental diabetes mellitus was assessed in anesthetized fasted (18-24 h) rats 4 wk after the administration of streptozotocin (65 mg/kg body wt) or its vehicle. Selective removal of pancreatic glucagon from the circulation was accomplished by the intravenous administration of a highly specific glucagon antiserum. Blood flow to the gastrointestinal tract and kidneys was measured with radioactive microspheres using the reference sample technique. Blood flows were increased by at least 60% in each segment of the gastrointestinal tract of diabetic animals compared with control rats. Glucagon antiserum had no effect on blood flows in the gastrointestinal tract of control animals. However, the antiserum produced a significant reduction in blood flow to the stomach (26%), duodenum (25%), jejunum (12%), and kidneys (16%) in diabetic rats. There was no change in blood flow to the ileum or colon of diabetic animals with antiserum administration. The results of this study support the hypothesis that glucagon mediates a portion of the hyperemia noted in the stomach, duodenum, and jejunum. However, glucagon does not appear to play a role in the genesis of the hyperemia noted in more distal segments of the gastrointestinal tract (ileum and colon). A possible role for glucagon in the maintenance of renal blood flow in diabetic rats is suggested.

Animals↗
PubMed1987

Quantitative assessment of villous motility.

A videomicroscopic method was used to quantitatively analyze villous motility in the dog small intestine. The frequency and duration of villous contractions (retractions) were measured in the duodenum, midjejunum, and distal ileum under controlled conditions. A pronounced gradient of villous motility was evident along the bowel. The duodenum exhibited the highest frequency (7.3 +/- 0.1/min) and longest duration (2.6 +/- 0.1 s) of contraction; the jejunum exhibited an intermediate frequency and duration of contraction (4.0 +/- 0.1/min, 2.1 +/- 0.1 s), and the lowest values were measured in the ileum (2.0 +/- 0.1/min and 1.8 +/- 0.1 s). In contrast to the retraction movements, the frequency of pendular villous movements (whipping, swaying movements without shortening) was highest in the jejunum and lowest in the duodenum. The frequency and duration of villous contractions (retractions) remained relatively constant over a 2-h observation period. Reducing mucosal surface temperature from 38 to 30 degrees C caused the frequency of contraction to fall by 33% and the duration to increase by 106%. Varying the suffusate pH within the physiological range of 5.0-7.4 produced no significant effects on jejunal villous motility. Suffusion with glucose (140 and 280 mM) failed to alter villous motility. However, amino acid (15 and 30 mM) and fatty acid (10 mM) solutions significantly increased contraction frequency by 30-50% and 90%, respectively. The videomicroscopic method provides useful quantitative information, which should extend current knowledge regarding the regulation and physiological importance of villous motility.

Amino Acids↗
PubMed1987

Intestinal hyperemia in experimental diabetes mellitus.

Intestinal blood flows were measured using the radioactive microsphere technique in anesthetized, fasted (18-24 h) rats 4 wk after administration of streptozotocin (65 mg/kg body wt) or its vehicle. Blood flow was increased along the length of the small bowel in diabetic rats relative to normal animals. In an attempt to define the mechanisms underlying the intestinal hyperemic response to diabetes, we employed an in situ, blood perfused, isolated rat jejunum-ileum preparation. Intestinal blood flow was increased by 37%, while intestinal vascular resistance was reduced by 39% in diabetic rats relative to control animals. Cross-perfusion of control intestinal preparations with arterial blood from diabetic rats produced a 30% increase in blood flow and a 24% reduction in vascular resistance. Increasing plasma osmolarity, plasma glucose concentration, or plasma glucagon concentration in control animals to levels measured in diabetic animals produced reductions in vascular resistance that were qualitatively similar to that seen in the diabetic intestine. Intestinal vascular sensitivity to norepinephrine was assessed by constructing dose-response curves in control and diabetic animals. The mean ED50 values for norepinephrine were increased in diabetic rats relative to control animals. These results indicate that the intestinal hyperemic response in diabetes may be related to increased levels of circulating vasodilators, including hyperosmolarity and glucagon, and a reduced vascular sensitivity to norepinephrine.

Animals↗
PubMed1987

Splanchnic circulatory changes during development of renal hypertension.

Total and regional splanchnic blood flows were measured with radiolabeled microspheres (15 micron) in one-kidney, one-clip renal hypertensive rats at 2, 4, and 6 wk after induction of hypertension. Arterial pressures (mean +/- SE, mmHg) for the normotensive rats (N) and age-matched hypertensive rats (H) were 110 +/- 5 and 114 +/- 6 at 2 wk, 104 +/- 4 and 148 +/- 13 at 4 wk, and 117 +/- 6 and 164 +/- 11 at 6 wk, respectively. Total splanchnic blood flow was increased in H compared with N at 4 wk but not at 2 or 6 wk. The blood flow changes among individual splanchnic organs varied in N and H. For example, at 2 and 4 wk, stomach, small intestine, large intestine, pancreas, hepatic artery, and portal venous blood flows in H were unchanged compared with N. At 6 wk, small intestinal and hepatic arterial blood flows were increased in H compared with N, and pancreatic blood flow was decreased. Vascular resistance was not different for any splanchnic organs between N and H at 2 wk, but it was elevated in H for all organs at 4 and 6 wk except for the hepatic artery. In another group of rats, the renal and superior mesenteric arteries (SMA) were instrumented with ultrasonic Doppler flow probes. Acute one-kidney, one-clip hypertension was produced by removing one kidney and mechanically reducing flow to the remaining kidney with a pneumatic occluder. After 2 h of stenosis, mean arterial pressure and SMA flow velocity was decreased by 6%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1986

Renal hyperemia in portal hypertension is not mediated by gastrointestinal peptides.

The objectives of this study were to characterize the time course of development of the renal hyperemia induced by chronic portal vein stenosis (PVS) in the rat, and to assess the possibility that vasoactive blood-borne gastrointestinal peptides mediate the renal hyperemia in established portal hypertension. Blood flow to the kidneys was measured with radioactive microspheres over a ten day time course. On day 2, no difference in renal blood flow (RBF) was observed in PVS rats as compared with controls. However, by day 4, RBF significantly increased by 35% in PVS vs. control animals. On day 6, the renal hyperemia in PVS rats reached a maximal value that was 42% higher than controls. A steady state hyperemia (approximately 40%) was maintained thereafter. Radioimmunoassay of plasma from control and established portal hypertensive rats (10 days samples) revealed that vasoactive intestinal polypeptide, substance P, cholecystokinin, gastrin, neurotensin, pancreatic polypeptide, beta-endorphin and peptide histidine-isoleucine amide are not elevated in arterial plasma of portal hypertensive rats. These data suggest that the renal hyperemia induced by chronic portal vein stenosis is apparent within 4 days of the onset of a hypertensive state and attains a steady state by day 8. Furthermore, at least eight blood-borne gastrointestinal peptides are not directly involved in the renal hyperemia associated with chronic portal hypertension.

Animals↗