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PubMed1993

Nitric oxide modulates responses to sensory nerve activation of the perfused rat mesentery.

The modulatory actions of nitric oxide on sensory nerves were investigated on dilator responses of the perfused rat mesentery to transmural nerve stimulation. N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, caused a significant augmentation of vasodilator responses to transmural nerve stimulation, an effect which was abolished by L-arginine. L-NAME had no effect on vasodilator responses to exogenous calcitonin gene-related peptide. In preparations without endothelium L-NAME still caused potentiation of vasodilator responses to transmural nerve stimulation. Methylene blue, an inhibitor of guanylate cyclase, also significantly enhanced vasodilator responses to transmural nerve stimulation. After pretreatment with diethyldithiocarbamate to inhibit superoxide dismutase, vasodilator responses to transmural nerve stimulation were also potentiated. This response was abolished by exogenous superoxide dismutase. These findings suggest that endogenous nitric oxide modulates, in an inhibitory fashion, the actions of sensory nerves in the rat mesentery. The results also suggest that endogenous superoxide dismutase may participate in the regulation of the actions of sensory nerves via control of cellular superoxide anion level.

Animals↗

PubMed1990

Effect of plasma from essential hypertensives on vascular tone of aortic strips, isolated perfused mesentery and isolated perfused kidney.

Different vascular models of normotensive Wistar rats, including aortic strips, isolated perfused mesentery and isolated perfused kidney, were used to study hemodynamic effects of plasma fractions obtained by gel filtration from the blood of essential hypertensive and normotensive subjects. Plasma fractions from essential hypertensives studied had been shown to increase blood pressure after intravenous injection in rats. In the aortic strips, 50 microliters of a hypertensive fraction (HF) elicited a calcium-dependent contraction of 0.14 +/- 0.035 mN (n = 20, p less than 0.05), which was inhibited by nifedipine, whereas tension of the strips was not significantly changed by normotensive fractions (NF) (n = 17). In the isolated perfused mesentery preparation, no significant change of perfusion pressure by HF or NF could be demonstrated (n = 10). In the isolated perfused kidney, a transient increase of perfusion pressure was induced by HF (19.5 +/- 16.6 mm Hg, n = 40, P less than 0.001) but not by NF. This increase was abolished in calcium-free, 2 mmol/l EGTA containing perfusion medium. The response was diminished, but not abolished by nifedipine. These data demonstrate vasopressor properties of plasma from essential hypertensives, which might be the consequence of a circulating vasoconstrictor substance in the blood of essential hypertensives.

Adult↗

PubMed1983

Effects of leukotriene C4 and prostaglandin E2 on the rat mesentery in vitro and in vivo.

Leukotriene C4 (LTC4) and Prostaglandin E2 (PGE2) have been studied for their effects on the rat mesentery in vitro and in vivo. Their effects on the norepinephrine (NE) induced vasoconstrictions in the above vascular bed have also been investigated. LTC4 (10(-10)M) and PGE2 (2.8 X 10(-7)M) produced no direct effects on the perfusion pressure in the isolated perfused rat mesentery. However, LTC4 (10(-10)M) produced constriction of the arterioles in vivo. PGE2 (2.8 X 10(-7)M) did not produce any direct effect on the microcirculation. Indomethacin, when superfused for 10 min. in a concentration of 7 X 10(-5)M, produced significant arteriolar constriction; this effect was reversed when PGE2 was added to the superfusing media containing indomethacin. LTC4, perfused in a concentration of 10(-10)M, produced a time - dependent inhibitory effect on NE induced vasoconstrictions in vitro whereas PGE2 perfusions (2.8 X 10(-7)M) potentiated the NE responses. This potentiating effect of PGE2 was inhibited by indomethacin. In contrast, the topical application of PGE2 in vivo attenuated NE responses of the mesenteric arterioles.

Animals↗

PubMed1983

Modulatory effects of substance P on norepinephrine induced vasoconstrictor responses in the rat mesentery.

1. The role of substance P (SP) in adrenergic transmission has been studied in the isolated perfused rat mesentery. 2. Intra-arterial perfusion of SP (4 x 10(-9) to 4 x 10(-7)M) produced a dose dependent potentiation of norepinephrine (NE) induced vasoconstrictor responses and a shift of the log dose--response curve to the left. 3. Saralasin, a specific antagonist of angiotensin II (ang. II) when perfused at a concentration of 3 x 10(-9)M did not change the NE responses as such. However, the potentiating effect of SP could not be demonstrated in the presence of saralasin. 4. Indomethacin, a prostaglandin (PG) synthetase inhibitor, when perfused at a concentration of 2.8 x 10(-6)M, markedly attenuated the vascular responses to NE, which could not be normalized by the addition of SP. 5. It appears that SP's potentiating effect on NE responses in the perfused rat mesentery simulates ang. II and not prostaglandins. A direct non-specific post synaptic sensitizing effect of SP on vascular smooth muscle cell, for its potentiating property, cannot be ruled out.

Animals↗

PubMed2000

Role of gap junctions in acetylcholine-induced vasodilation of proximal and distal arteries of the rat mesentery.

We have previously shown that myoendothelial gap junctions are more prevalent in distal than in proximal arteries of the rat mesentery. In the present study we have investigated the role of gap junctions in the mechanism of action of endothelium-derived hyperpolarizing factor (EDHF) in these same vessels following relaxation with acetylcholine. Arteries were pre-constricted with phenylephrine and concentration response curves to acetylcholine were constructed in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME; 10(-5) M) and indomethacin (10(-5) M) to prevent effects due to the release of nitric oxide and prostacyclins. Nitric oxide was found to have only a small role in the relaxation of the proximal vessels and was not involved in the relaxations of the distal vessels. 18 alpha-Glycyrrhetinic acid (10(-5) M), a putative gap junction uncoupler, significantly reduced acetylcholine-induced relaxations by 50% in both proximal and distal vessels. Potassium channel antagonists, tetraethylammonium chloride (TEA; 10(-3) M) and barium chloride (10(-4) M), together abolished the dilatory response in the proximal mesenteric arteries, but did not completely block responses in the distal arteries. The data suggest that gap junctions contribute significantly to the acetylcholine-induced relaxation in both proximal and distal arteries of the rat mesentery. We hypothesize that the absence of a correlation between the role of gap junctions and the incidence of myoendothelial gap junctions in these same vessels is due to significant effects of the inhibitors on gap junctions located in the smooth muscle layers of the larger vessels.

Acetylcholine↗

PubMed1997

Fluoroaluminate induces rapid release of endothelin-1 in the isolated perfused arterial and venous vessels of the rat mesentery.

1. Endothelin-1 (ET-1) production from endothelial cells is generally believed to be a process that happens over the course of hours. 2. When fluoroaluminate (AIF-4) was infused in the isolated perfused arterial and venous vessels of the rat mesentery there was an increase in perfusion pressure on both sides. 3. Treatment of mesentery with the endothelin receptor antagonists FR 139317 (ETA receptor selective) or PD 145065 (ETA-ETB receptor nonselective) caused inhibition on both the arterial and venous sides, suggesting that response is mediated predominantly by endothelin-1 through ETA receptors. 4. Endothelial denudation attenuated changes in perfusion pressure of mesenteric circulation generated by fluoroaluminate, but not those caused by exogenously added PGF2 alpha. 5. Our data demonstrate that there is an immediate release of endothelin-1 following fluoroaluminate infusion which could be partially mediated by activation of phospholipase C.

Aluminum↗

PubMed2001

Analysis of increased leukocyte ratio induced by tumor necrosis factor-alpha using several inhibitors in the undisturbed microcirculation of the rat mesentery.

Increased leukocyte ratio induced by intraperitoneal injection of TNF-alpha was analyzed in undisturbed rat mesentery venules, a long-term experimental model. TNF-alpha induced a biphasic increase in PMNL ratio in the mesentery venules; in particular, there was a large increase in PMNL ratio 3 h after injection of TNF-alpha. Anti-P and anti-L-selectin compounds, fucoidin and dextran sulfate, inhibited the PMNL ratio by about 40%. Dexamethasone completely inhibited the increased ratio. These results suggest that all selectins may be involved in the increased ratio, i.e. rolling and adhesion reaction.

Animals↗

PubMed1999

Influence of local haemodynamics on leucocyte rolling and chemoattractant-induced firm adhesion in microvessels of the rat mesentery.

Tissue hyperaemia, oedema formation and leucocyte accumulation are characteristic features of the inflammatory process referable to changes at the microcirculatory level. Here, we used intravital fluorescence video microscopy to assess relationships among haemodynamical parameters, leucocyte rolling, and chemoattractant-induced firm adhesion in small venules (13-24 microM) of the rat mesentery. The rolling leucocyte flux in these vessels was directly proportional to the total leucocyte flux (r = 0.76, P < 0.001), which in turn closely correlated to the venular blood flow (r = 0.77, P < 0.001). Consequently, the rolling to total leucocyte flux fraction, averaging 39 +/- 15%, did not vary with the blood flow and showed no correlation to either blood flow velocity (r = -0.15, P = 0.42) or wall shear rate (r = -0.06, P = 0.77), indicating that the extent of leucocyte rolling is not primarily dependent on the fluid viscous drag at physiological blood flow rates in vivo. Stimulation of the mesentery with the chemoattractant fMLP (10(-6) M) induced firm adhesion of rolling leucocytes. It was found that the number of adherent leucocytes in individual vessels was directly related to the rolling leucocyte flux (r = 0.78, P < 0.001) and hence to the venular blood flow (r = 0.47, P < 0.05), while there was no correlation to the wall shear rate (r = 0.27, P = 0.24). The dependence of the firm adhesive response on the blood flow level and the delivery rate of leucocytes was confirmed at the whole organ level. Thus, leucocyte accumulation in rat skin lesions was markedly enhanced when a vasodilator was co-administered with the chemotactic stimulus compared with chemotactic stimulation alone. The data indicate that, within a physiological blood flow range, the leucocyte response to chemotactic stimulation is largely independent of the prevailing hydrodynamic shear forces. Instead, manifestation of the firm adhesive response, because of its dependence on the preceding rolling interaction, is clearly related to the blood flow level in the microvessels, which emphasizes the significance of tissue hyperaemia in inflammation.

Animals↗

PubMed1993

Transforming growth factor-beta enhances connective tissue repair in perforated rat mesentery but not peritoneal macrophage chemotaxis.

The perforated rat mesentery model was used to study the effect of transforming growth factor-beta (TGF-beta) on connective tissue repair and influx of macrophages into the peritoneal cavity during such repair. Sprague-Dawley rats were laparotomized, and mesenteric wounds were made with a scalpel. A daily intraperitoneal injection of 0.5 microg TGF-beta was given for either 2 or 4 days. After 1 to 10 days, the animals received an intravenous injection of tritium-labeled thymidine before decapitation. Macrophages were collected by peritoneal washing, and the number of closed perforations was counted. Peritoneal cells were quantitated and a labeling index was determined by autoradiography. TGF-beta given for either 2 (p < 0.001) or 4 (p < 0.004) days accelerated closure of perforations on days 3 to 7 after injury. Laparotomy as such significantly increased leukocyte influx (p < 0.004), as well as macrophage-labeling index (p < 0.02). However, TGF-beta did not significantly influence either leukocyte influx or macrophage-labeling index. We concluded that TGF-beta significantly enhances connective tissue repair in this perforated rat mesentery model and that TGF-beta-induced stimulation of repair is not caused by an increased influx of macrophages into the peritoneal cavity.

Journal Article↗

PubMed2004

Analysis of leukocyte rolling and migration--using inhibitors in the undisturbed microcirculation of the rat mesentery--on inflammatory stimulation.

AIM: Our aim was to develop a method of migration analysis using the undisturbed microcirculation of rat mesentery, and using the new method, analyze leukocyte migration in casein-induced inflammation. METHOD: Sprague Dawley (SD) rats were injected with tumor necrosis factor (TNF) alpha, interleukin (IL)-1alpha, or casein intraperitoneally. Following this, the rats were sacrificed and the mesentery tissue removed was fixed and stained with Giemsa. The leukocytes were counted as a rolling index in the venules and as a migration index in the perivascular area. RESULTS: There was no relation between the diameter of venules and leukocyte migration. The time change curves of leukocyte activity in casein inflammation show about a 1 h difference between rolling and migration. From inhibitor experiments of casein-induced migration at 2 h, it has been suggested that selectin-related rolling is necessary. Platelet-activating factor (PAF) also appears partially involved. CONCLUSION: The improved undisturbed microcirculation method is helpful not only for rolling analysis but also in analysis of leukocyte migration. Casein inflammation analyzed using this method revealed that rolling is necessary and also suggested that partial involvement of PAF is necessary for pathogenesis of leukocyte extravasations.

Animals↗

PubMed2004

An adenovirus-mediated gene-transfer model of angiogenesis in rat mesentery.

OBJECTIVE: To develop an adenovirus-mediated angiogenesis model, dependent on VEGF, in a system amenable to functional characterization. METHODS: Adenovirus (AdV) expressing VEGF (Ad-VEGF) or GFP (Ad-EGFP) (1-3.3 x 10(8) TCID50/mL), and Monastral blue were injected into the fat pad on either side of a mesenteric connective tissue panel of halothane-anesthetized male Wistar rats after intravital microscopic imaging. The intestine was replaced in the animal, the laparotomy was sutured, and the animal was allowed to recover. Six days later, the same connective tissue panel was identified from the Monastral blue depot and the mesentery was imaged as before, and then excised, fixed, and stained for endothelial cells (GSL isolectin-1B4), proliferating cells, VEGF, VEGF-R2, and actin. The increase in fractional microvascular area (FVA) was measured, and proliferating cell density, sprout density, vessel branch point density, vessel density, and mean vessel length were determined. RESULTS: AdVEGF injection significantly increased the fractional vessel area (2.9 +/- 0.4-fold), proliferating endothelial cell density (1.7 +/- 0.1-fold), sprout density (3.1 +/- 0.3-fold), branch point density (1.9 +/- 0.1-fold), and the microvessel density (1.4 +/- 0.1-fold), and decreased the mean vessel length (0.69 +/- 0.04-fold). VEGF-R2 staining was evident near sprouting tips of endothelial cells, but not on the tip itself, and evidence for arteriogenesis was observed as well as clear evidence of angiogenesis. CONCLUSIONS: Ad-VEGF injection into the fat pad of the rat induced significant angiogenesis in the mesentery. This two-dimensional model of VEGF-induced angiogenesis is amenable to physiological, biochemical, and molecular assessment and may be a useful tool to help understand mechanisms of angiogenesis.

Adenoviridae↗

PubMedDate not supplied

Nitric oxide measurements in rat mesentery reveal disrupted venulo-arteriolar communication in diabetes.

OBJECTIVE: Arteriolar tone is partially controlled by diffusing mediators released by closely paired venules and is reported to depend on venular shear and venular leukocyte adherence. In healthy rat mesentery, venule-initiated arteriolar dilation and consequent enhanced capillary flow appear to be tightly regulated by nitric oxide (NO). In contrast, diabetes inhibits NO-dependent vasodilation and is associated with dysfunctional microcirculation. The objective of this study was to investigate venule-dependent NO in diabetes. METHODS: Arteriolar and venular wall concentrations of NO were measured in control and diabetic (streptozotocin-induced) rat mesentery with fluorescent diaminofluorescein-2-diacetate (DAF-2-DA); tissue NO was measured with DAF-2. Venular leukocyte adherence and microvascular shear rates were also measured. RESULTS: Microvascular NO in diabetic rats was found to be significantly lower (<50%) than in controls. In normal rats, arteriolar NO demonstrated a positive correlation with venular NO and venular shear, and a negative correlation with venular leukocyte adherence. Diabetes eliminated all these correlations. No correlation was present between arteriolar NO and arteriolar shear in either normal or diabetic rats. CONCLUSIONS: Arteriolar NO appears to be enhanced by venular shear in normal but not in diabetic rats. This dysfunction could contribute to poor capillary perfusion in diabetes.

Animals↗

PubMed2002

In vivo PIV measurement of red blood cell velocity field in microvessels considering mesentery motion.

As endothelial cells are subject to flow shear stress, it is important to determine the detailed velocity distribution in microvessels in the study of mechanical interactions between blood and endothelium. Recently, particle image velocimetry (PIV) has been proposed as a quantitative method of measuring velocity fields instantaneously in experimental fluid mechanics. The authors have developed a highly accurate PIV technique with improved dynamic range. spatial resolution and measurement accuracy. In this paper, the proposed method was applied to images of the arteriole in the rat mesentery using an intravital microscope and high-speed digital video system. Taking the mesentery motion into account, the PIV technique was improved to measure red blood cell (RBC) velocity. Velocity distributions with spatial resolutions of 0.8 x 0.8 microm were obtained even near the wall in the centre plane of the arteriole. The arteriole velocity profile was blunt in the centre region of the vessel cross-section and sharp in the near-wall region. Typical flow features for non-Newtonian fluid were shown. Time-averaged velocity profiles in six cross sections with different diameters were compared.

Animals↗

PubMed1998

Müllerian cysts of the mesentery and retroperitoneum: a case report and literature review.

Müllerian cyst of the mesentery and retroperitoneum is an extremely rare disease entity. Only two photomicrograph reports have been published. A 47-year-old Korean woman presented with abdominal distention. A mesenteric cystic mass, measuring 25 x 23 x 18 cm, was found between the liver and right adnexa without any connection with adjacent organs. The cyst was multilocular with gray-white, rubbery walls of relatively uniform 0.2 cm thickness. Microscopically, the lining cells were ciliated and cuboidal to low columnar with an incomplete lining of smooth muscle bundles, adipose tissues, lymphovascular spaces, and lymphocytic aggregates. Ultrastructurally, the lining cells had intercellular junctions, and cilia or microvilli on their luminal surface. The lining cells were immunoreactive for cytokeratin, epithelial membrane antigen and vimentin. To the best of our knowledge, this is the first demonstration of ultrastructural and immunohistochemical findings of Müllerian cyst of the mesentery and retroperitoneum in the English literature.

Cysts↗

PubMed1989

The effects of ionophore A23187 on permeability of the frog mesentery microvasculature.

The effects of the divalent cation ionophore A23187, upon microvascular permeability have been investigated in single perfused capillaries and venules in the mesenteries of pithed frogs. In all experiments, the vessels were perfused with Ringer solutions containing the macromolecules Ficoll 70 (40 mg ml-1) and bovine serum albumin (10 mg ml-1). Hydraulic permeability (Lp) of the vessel walls and the effective osmotic pressure (sigma delta pi) exerted across them by the perfusate macromolecules were estimated by the method of Michel (1980). In eleven experiments addition of A23187 to the perfusate raised Lp from a mean value (+/- S.E.M.) of 4.76 (+/- 1.05) x 10(-7) cm s-1 cmH2O-1 to one of 11.97 (+/- 1.96) x 10(-7) cm s-1 cmH2O-1 and reduced sigma delta pi from a mean (+/- S.E.M.) of 16.5 (+/- 2.01) cmH2O to one of 7.6 (+/- 1.93) cmH2O. The effects of A23187 on Lp and sigma delta pi were reversible. A23187 was found to increase Lp and reduce sigma delta pi after the mesentery had been exposed to compound 48/80 to degranulate the mast cells two or more hours previously. A23187 also appeared to be effective in raising Lp and lowering sigma delta pi in the absence of Ca2+ ions from the perfusate and superfusate. The ionophore was found to reduce permeability, however, when Mg2+ ions were removed from the perfusate and superfusate both in the absence and in the presence of Ca2+. This reduction in permeability could be converted into an increase in Lp and fall in sigma delta pi if Mg2+ were restored to the superfusate. It is concluded that A23187 increases vascular permeability in a reversible manner and that Mg2+ ions in the extracellular fluids are necessary for its action.

Animals↗

PubMed1983

Development of sympathetic innervation to proximal and distal arteries of the rat mesentery.

The changes which occur during the post-natal development of sympathetic innervation to proximal and distal arteries of the rat mesentery have been examined using intracellular recording and histochemical techniques. In the youngest animals examined, single perivascular stimuli initiated slow depolarizing potentials which were not calcium-dependent. After day 4, single stimuli failed to initiate membrane potential changes in a proportion of preparations. This stage coincided with the period of extensive ramification of sympathetic nerve fibres over the surface of the arterioles. From day 9 onwards, membrane potential changes were again initiated by single stimuli in the distal arteries. These responses were distinct from those recorded from the younger animals and in many ways resembled excitatory junction potentials recorded from the arteries of mature animals. There was a gradient in the development of the innervation to the arteries of the rat mesentery, with that to the distal vessels maturing earlier than that to the more proximal vessels.

Action Potentials↗

PubMed1983

Arteriolar responses to elevation of venous and arterial pressures in cat mesentery.

These studies were undertaken to determine the importance of metabolic (flow-dependent) and myogenic (pressure-dependent) factors in the response of arterioles to changes in intravascular pressure. The response of 26 arterioles in the isolated cat mesentery to increased venous and arterial pressure was studied by measuring changes of arteriolar diameter, red blood cell velocity, and intravascular pressure. Circumferential wall tension and volume flow in the arterioles were calculated. The fraction of the arteriolar responses to intravascular pressure elevation that could be attributed only to a myogenic response in which wall tension is regulated varied from 20 to 56%, depending on the method of pressure elevation. The largest fraction of the response attributable to a myogenic mechanism (ignoring the contributions of flow) varied from 50 to 93%. The fraction of the responses attributable only to flow dependency varied from 0 to 23%, whereas the largest fraction attributable to this mechanism varied from 18 to 73%, depending on the method of pressure elevation. It is concluded that, in cat mesentery, both metabolic and myogenic mechanisms appear to contribute to local regulation of flow with elevation of intravascular pressure, but other factors cannot be excluded.

Animals↗

PubMed1990

Anionic fixed charges in the fenestrated capillaries of the mouse mesentery.

Previous studies showed the existence of submesothelial fenestrated capillaries in the human parietal and rabbit diaphragmatic peritoneum, as well as in the mouse mesentery. The present study demonstrates the presence of electronegative fixed charges at the luminal aspect of endothelial cells, as well as long the subendothelial basement membrane of the fenestrated capillaries of the mouse mesentery. This situation will eventually preclude the transfenestral passage of anionic plasma proteins. On the other hand, fenestrated capillaries are much more permeable to water and small-molecular-size solutes than those of the continuous type. Therefore, the high hydraulic conductivity of fenestrae may well imply that a substantial part of water and small solutes leave the blood compartment through the fenestral channels.

Animals↗