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Results for “Microvessels”

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At least 667 records · Page 37Linked to original sources

PubMed1990

Glucose is required to maintain ATP/ADP ratio of isolated bovine cerebral microvessels.

Isolated bovine cerebral microvessels (ICMV) were incubated with different metabolic fuels to determine the effect of each of them on microvessel energy state. With no fuel added to the medium, the ATP/ADP generally decreased from initial values of 1.5-3 down to 1-1.5 over 4 h; the ATP content also declined approximately 50%. In contrast, with glucose present, the ATP/ADP increased, and the ATP content was maintained. Pyruvate, beta-hydroxybutyrate, glutamate, and oleate were ineffective; oleate added together with carnitine gave some improvement but less than with glucose. Oxygen consumption by ICMV did not differ appreciably in fuel-free or glucose-containing medium. Addition of an inhibitor of fatty acid oxidation, 2-tetradecylglycidate, depressed the ATP/ADP. These results suggest that ICMV require glycolysis to maintain both their content of ATP and their ATP/ADP. They also suggest that endogenous lipid is an important fuel for isolated microvessels.

Adenosine Diphosphate↗

PubMed2003

Structural mechanisms of acute VEGF effect on microvessel permeability.

To investigate the ultrastructural mechanisms of acute microvessel hyperpermeability by vascular endothelial growth factor (VEGF), we combined a mathematical model (J Biomech Eng 116: 502-513, 1994) with experimental data of the effect of VEGF on microvessel hydraulic conductivity (L(p)) and permeability of various-sized solutes. We examined the effect of VEGF on microvessel permeability to a small solute (sodium fluorescein, Stokes radius 0.45 nm), an intermediate solute (alpha-lactalbumin, Stokes radius 2.01 nm), and a large solute [albumin (BSA), Stokes radius 3.5 nm]. Exposure to 1 nM VEGF transiently increased apparent permeability to 2.3, 3.3, and 6.2 times their baseline values for sodium fluorescein, alpha-lactalbumin, and BSA, respectively, within 30 s, and all returned to control within 2 min. On the basis of L(p) (DO Bates and FE Curry. Am J Physiol Heart Circ Physiol 271: H2520-H2528, 1996) and permeability data, the prediction from the model suggested that the most likely structural changes in the interendothelial cleft induced by VEGF would be a approximately 2.5-fold increase in its opening width and partial degradation of the surface glycocalyx.

Algorithms↗

PubMed2003

Cholinergic regulation of pericyte-containing retinal microvessels.

The aim of this study was to test the hypothesis that the neurotransmitter acetylcholine regulates the function of pericyte-containing retinal microvessels. A vasoactive role for acetylcholine is suggested by the presence of muscarinic receptors on pericytes, which are abluminally positioned contractile cells that may regulate capillary perfusion. However, little is known about the response of retinal microvessels to this neurotransmitter. Here we assessed the effects of cholinergic agonists on microvessels freshly isolated from the adult rat retina. Ionic currents were monitored via perforated patch pipettes; intracellular Ca(2+) levels were quantified with the use of fura 2, and microvascular contractions were visualized with the aid of time-lapse photography. We found that activation of muscarinic receptors elevated pericyte calcium levels, increased depolarizing Ca(2+)-activated chloride currents and caused pericytes to contract in a Ca(2+)-dependent manner. Most contracting pericytes were near capillary bifurcations. Contraction of a pericyte caused the adjacent capillary lumen to constrict. Thus acetylcholine may serve as a vasoactive signal by regulating pericyte contractility and thereby capillary perfusion in the retina.

Acetylcholine↗

PubMed2003

Mechanism of glutamate stimulation of CO production in cerebral microvessels.

Dilation of piglet pial arterioles to glutamate involves carbon monoxide (CO) produced from heme by heme oxygenase-2 (HO-2). Piglet cerebral microvessels and endothelial and smooth muscle cells grown on microcarrier beads were used to address the hypothesis that glutamate increases endothelial CO production by increasing HO-2 catalytic activity. CO was measured by gas chromatography/mass spectrometry. Glutamate increased CO production from endogenous heme by cerebral microvessels, endothelial cells, and smooth muscle cells. Glutamate increased the conversion of exogenous heme to CO. Protein tyrosine kinase inhibition blocked glutamate stimulation of CO production. Inhibition of protein tyrosine phosphatases stimulated CO production. Conversely, neither phorbol myristate acetate nor H-7 changed glutamate stimulation of CO production. The mechanism of HO-2 stimulation by glutamate appears to be independent of cytosolic Ca, because stimulation of CO production by glutamate was the same in Careplete medium, Ca-free medium with ionomycin, and Careplete medium with ionomycin. Therefore, glutamate appears to increase HO-2 catalytic activity in cerebral microvessels via a tyrosine kinase mediated pathway.

Animals↗

PubMed1981

Methods for isolation, cannulation, and in vitro study of single microvessels.

A method is described for the isolation and cannulation of microvessels (12-112 micrometers) that permits study, in vitro, of their physiology and pharmacology. Vessels from the hamster cheek pouch, testis, and mesentery and from rat brain have been isolated at 4 degrees C with specially prepared instruments and viewed with an inverted microscope. The vessels were cannulated at one end by equipment developed for renal tubular perfusion. The uncannulated end of the vessel is sealed, and experiments on reactivity and mechanics are carried out at fixed intravascular pressures. The isolated microvessels studied have a modulus of elasticity that is consistent with that observed in large vessels, and they display similar maximal active tension development (approximately 10(6) dyn/cm2). Reactivity to norepinephrine, acetylcholine, and adenosine are in the normal range for microvessels. Spontaneous tone is present, as evidenced by stable tonic contractions as well as phasic contractions in the frequency range of 3-30/min. The vessels display stress activation (myogenic response) consisting of contraction in response to increased intraluminal pressure. Our findings suggest that this preparation will be very useful in elucidating the physiology and pharmacology of the resistance vessels in the terminal vasculature.

Animals↗

PubMed1990

Graded modulation of frog microvessel permeability to albumin using ionophore A23187.

We investigated the exchange of water and macromolecules across venular microvessels after permeability was increased. Quantitative fluorescence microscopy was used to measure albumin permeability coefficients in individually perfused microvessels of decerebrate frogs. Control permeability coefficient was 2.3 +/- 0.25 X 10(-7) cm/s. Solvent drag increased the apparent solute permeability coefficient (Ps) by 0.57 +/- 0.05 X 10(-7) cm/s for each cmH2O increase in microvessel pressure. The divalent cation ionophore A23187 (0.1-5 microM) produced a transient increase in Ps to a peak value (within 1-3 min), followed (after 4-8 min) by a sustained increase in permeability (16-34% of peak values). Peak values of Ps were 13 and 80 times control for 0.1 and 5 microM A23187, respectively. Both diffusion and solvent drag contributed to the sustained increase in Ps. The equivalent pore radius of the structures determining diffusion and solvent drag was less than or equal to 25 nm during the sustained increase in permeability, smaller than observed gaps between adjacent endothelial cells. The basement membrane and a fibrous matrix secreted by endothelial cells into the gaps may offer resistance to exchange in the high permeability state.

Animals↗

PubMed1990

Measurement of cytoplasmic calcium in single microvessels with increased permeability.

We investigated the hypothesis that an increase in cytoplasmic calcium ion concentration, [Ca2+]i, is one of the mechanisms responsible for increased microvessel permeability. We loaded the cells forming the walls of individually perfused microvessels in frog mesentery with fura-2 and measured [Ca2+]i in the control state and after adding the Ca2+ ionophore ionomycin to the perfusate. [Ca2+]i in the control state was 65 +/- 6 nM and increased to an initial peak of 285 +/- 29 nM after 1-3 min. After 4, 6, and 10 min, [Ca2+]i was 199 +/- 18, 163 +/- 16, and 129 +/- 9 nM, respectively. [Ca2+]i fell back to 77 +/- 7 nM after ionophore was removed. In similar experiments, hydraulic conductivity (Lp) increased to a peak of 9.5 times control after 1-3 min, then fell to 2.0 times control after 6 min. Lp remained elevated at this level for as long as ionophore was present in the perfusate. [Ca2+]i modulates the initial and sustained phases of the permeability increase. Both processes depend on external Ca2+ influx. Our experiments provide the first direct measurement of [Ca2+]i during a change in the permeability of an intact microvessel.

Animals↗

PubMed1992

Differences and similarities in albumin and red blood cell flows through cerebral microvessels.

The hypothesis that microvessels in brain parenchyma are continuously perfused by plasma but intermittently perfused by red blood cells (RBCs) was tested in awake Sprague-Dawley rats. The microvascular distribution volumes of radioiodinated serum albumin (RISA) and 51Cr- and 55Fe-labeled RBCs were measured for periods from 15 s to 30 min. Local cerebral blood flow (LCBF) was assessed by the iodoantipyrine technique. The RISA and RBC distribution volumes were constant in the 12 areas studied from 15 s onward. These data fit a model of continuous plasma flow with intermittent RBC flow (and thus support the hypothesis), but they are also consistent with other models, e.g., continuous flow of both plasma and RBCs through all perfused microvessels. In parallel with LCBF, microvascular blood volume varied greater than 10-fold among brain areas. Relative to arterial hematocrit, microvascular hematocrits were low, which indicates that the passage of RBCs through parenchymal microvessels is more rapid than that of RISA. This could be the result of both the Fahraeus effect and intermittent RBC flow.

Animals↗

PubMed1994

Formation and action of a P-450 4A metabolite of arachidonic acid in cat cerebral microvessels.

The purpose of this study was to determine whether arachidonic acid can be converted to 20-hydroxyeicosatetraenoic acid (HETE) by P-450 enzymes in cat cerebral microvasculature, to identify the P-450 isoforms responsible for the formation of this metabolite, and to characterize the vasoactive effects of 20-HETE on these vessels. Cerebral microvessels were isolated by filling them with a suspension of magnetized iron oxide (particle size = 10 microns) and separated from minced cerebral cortical tissue using a magnet. Cat cerebral microvessels were homogenized and incubated with [14C]arachidonic acid (AA), and cytochrome P-450-dependent metabolites of AA were separated by reverse-phase high-pressure liquid chromatography. A major metabolite that coeluted with synthetic 20-HETE was identified. The formation of this metabolite was dependent on NADPH and was inhibited by 17-octadecynoic acid (ODYA), a specific suicide-substrate inhibitor of the omega-hydroxylation of AA by P-450 enzymes. Western blot analysis confirmed the presence of a P-450 enzyme of the 4A gene family in cat cerebral microvessels. Gas chromatography/mass spectrometry analysis revealed that this metabolite has an identical mass-to-charge ratio (391 m/z) as that of standard 20-HETE. Exogenous 20-HETE constricted pressurized cat pial arteries in a concentration-dependent manner with a threshold concentration of < 1.0 nM. 20-HETE (1 nM) inhibited the activity of a 217-pS K+ channel recorded in cell-attached patches of isolated cat cerebral microvascular muscle cells. Blockade of endogenous P-450 activity with 17-ODYA markedly increased the activity of the 217 pS K+ channel in these cells, an action that was completely reversed by a nanomolar concentration of 20-HETE, suggesting that 20-HETE might be an endogenous modulator of the 217 pS K+ channel in cerebral arterial muscle cells. These results demonstrate the presence of P-450 4A enzyme activity in the cerebral microvasculature of the cat that converts AA to 20-HETE. The potent vasoconstrictor effects of 20-HETE on cerebral vessels suggests that metabolites of P-450 enzymes of the 4A gene family could play an important role in regulating cerebral microvascular tone.

Animals↗

PubMed1996

Oxygen saturation and pH changes in cremaster microvessels of the rat.

Recent studies have shown a considerable extent of diffusive O2 transfer from precapillary vessels, but the occurrence of O2 influx into postcapillary vessels (diffusive shunting) is still controversial. In this study, we investigated diffusive shunting between pre- and postcapillary vessels in muscle tissue and pH changes in the microvessels in an attempt to determine the physiological significance of the parallel arrangement of arterial and venous vessels in tissue oxygenation. We used rat cremaster muscles and controlled the breathing of anesthetized rats using urethane with FIO2 set at 0.3 and 0.12. We employed a noninvasive spectrophotometric method of measuring pH, using a pH-sensitive dye (1-hydroxypyrene-3,6,8-trisulfonic acid) and the O2 saturation level of hemoglobin (SO2) in microvessels from small arteries down to arterioles and from venules up to small veins. At FIO2 0.30, pH significantly decreased from 7.39 +/- 0.02 to 7.26 +/- 0.05 (SD) in precapillary vessels and remained close to constant during passage through postcapillary vessels. At FIO2 0.12, pH decreased from 7.36 +/- 0.03 to 7.01 +/- 0.06 in precapillary vessels and then increased in postcapillary vessels from 6.75 +/- 0.19 to 7.27 +/- 0.08. At FIO2 0.30, SO2 decreased from 98.6 +/- 5.4 to 64.2 +/- 4.5% in precapillary vessels and increased from 62.5 +/- 6.5 to 89.4 +/- 4.1% in postcapillary vessels. At FIO2 0.12, SO2 decreased from 47.0 +/- 5.5 to 25.1 +/- 3.8% in precapillary vessels and remained close to constant in postcapillary vessels. In conclusion, during hyperoxia, diffusive shunting of O2 was enhanced, and during hypoxia, acid was accumulated in peripheral vessels. It is speculated that acid accumulated due to back-diffusion of CO2 from venous to arterial microvessels, liberating O2 bound to hemoglobin via the Bohr effect. The diffusive shunting of O2 and counterdiffusion and accumulation of CO2 may contribute to the homeostasis of tissue oxygenation levels.

Abdominal Muscles↗

PubMed2003

Selectin-dependent rolling and adhesion of leukocytes in nicotine-exposed microvessels of lung allografts.

The interaction of circulating leukocytes with lung microvessels is a critical event in the recruitment of effector cells into the interstitial tissue during episodes of inflammation, including smoking-induced chronic airway disease. In the present study, murine lung tissue transplanted into a dorsal skinfold window chamber in nude mice was used as a model system to study nicotine-induced leukocyte trafficking in vivo. The revascularized lung microvessels were determined to be of pulmonary origin based on their ability to constrict in response to hypoxia. We demonstrated that nicotine significantly enhanced rolling and adhesion of leukocytes within lung microvessels comprising arterioles and postcapillary venules in a dose-dependent manner, but failed to induce leukocyte emigration. Nicotine-induced rolling and adhesion was significantly higher in venules than in arterioles. Treatment of mice with monoclonal antibodies (MAbs) against L-, E-, or P-selectin after exposure of lung allografts to nicotine resulted in variable but significant inhibition of nicotine-induced rolling, whereas nicotine-induced subsequent adhesion was inhibited by MAbs against L- and P-selectin but not E-selectin. Exposure of lung allografts to nicotine along with PD-98059, a mitogen-activated protein kinase (MAPK)-specific inhibitor, resulted in significant inhibition of nicotine-induced rolling and adhesion. In vitro, exposure of murine lung endothelial cells to nicotine resulted in increased phosphorylation of mitogen-activated/extracellular signal-regulated protein kinase 1/2, which could be blocked by PD-98059. Overall, these results suggest that nicotine-induced inflammation in the airways could potentially be due to MAPK-mediated, selectin-dependent leukocyte-endothelial cell interactions in the lung microcirculation.

Animals↗

PubMed2000

Reversibility of increased microvessel permeability in response to VE-cadherin disassembly.

We determined the role of vascular endothelial (VE)-cadherin complex in regulating the permeability of pulmonary microvessels. Studies were made in mouse lungs perfused with albumin-Krebs containing EDTA, a Ca(2+) chelator, added to study the VE-cadherin junctional disassembly. We then repleted the perfusate with Ca(2+) to restore VE-cadherin integrity. Confocal microscopy showed a disappearance of VE-cadherin immunostaining in a time- and dose-dependent manner after Ca(2+) chelation and reassembly of the VE-cadherin complex within 5 min after Ca(2+) repletion. We determined the (125)I-labeled albumin permeability-surface area product and capillary filtration coefficient (K(fc)) to quantify alterations in the pulmonary microvessel barrier. The addition of EDTA increased (125)I-albumin permeability-surface area product and K(fc) in a concentration-dependent manner within 5 min. The permeability response was reversed within 5 min after repletion of Ca(2+). An anti-VE-cadherin monoclonal antibody against epitopes responsible for homotypic adhesion augmented the increase in K(fc) induced by Ca(2+) chelation and prevented reversal of the response. We conclude that the disassembled VE-cadherins in endothelial cells are mobilized at the junctional plasmalemmal membrane such that VE-cadherins can rapidly form adhesive contact and restore microvessel permeability by reannealing the adherens junctions.

Adherens Junctions↗

PubMed1999

Nitric oxide differentially attenuates microvessel response to hypoxia and hypercapnia in injured lungs.

The issue of whether the acinar microvessel response to alveolar hypoxia and hypercapnia is impaired in injured lungs has not been vigorously addressed, despite the importance of knowing whether it is or not when treating patients with serious lung injury in terms of permissive hypercapnia. Applying a real-time laser confocal luminescence microscope, we studied hypoxia- and hypercapnia-induced changes in the diameter of the intra-acinar arterioles, venules, and capillaries of isolated rat lungs harvested from animals exposed for 48 h to 21% O(2) (group N) or 90% O(2) (group H). Measurements were made with and without inhibition of nitric oxide (NO) synthase (NOS) by N(omega)-nitro-L-arginine methyl ester or of cyclooxygenase (COX) by indomethacin at different basal vascular tones evoked by thromboxane A(2) (TXA(2)) analog. Hypoxia in the absence of TXA(2) contracted arterioles in group N but not in group H. Attenuated hypoxia-induced arteriole constriction was restored almost fully by inhibiting NOS and partially by inhibiting COX. Hypercapnia induced venule dilation in group N, but did not dilate venules in group H, irrespective of TXA(2). NOS inhibition in hypercapnia unexpectedly enhanced venule and arteriole dilation in group H. These responses no longer occurred when NOS and COX were inhibited simultaneously. In conclusion, microvessel reactions to hypoxia and hypercapnia are abnormal in hyperoxia-injured acini, in which NO directly attenuates hypoxia-induced arteriole constriction, whereas COX inhibited by excessive NO impedes hypercapnia-induced microvessel dilation.

Animals↗

PubMed1998

Functional diameters of alveolar microvessels at high lung volume in zone II.

To estimate the functional diameter of alveolar microvessels, we perfused isolated rat lungs with fluorescent latex particles (1 diameter/lung) at inflation, pulmonary arterial, and left atrial pressures of 25, 30, and 0 cmH2O, respectively. We used confocal microscopy to count latex particles within septal microvessels and flow cytometry to count particle concentrations in venous outflow. We found 1-, 2-, and 4-micron-diameter particles within septal vessels of 45 +/- 12, 31 +/- 12, and 25 +/- 9%, respectively, of examined alveoli. Particles of 5-micron diameter were absent from septal vessels but were present within a small percentage of corner vessels. Particle concentrations in the venous outflow for 1-, 2-, 4-, and 5-micron-diameter particles were 54 +/- 28, 67 +/- 32, 2.2 +/- 0.3, and 0.4 +/- 0.3%, respectively, of the arterial inflow. Particles with diameters of 6 or 10 micron were absent from venous outflow. Our results suggest that, under these conditions, the functional diameter of the septal microvessels is approximately 4 micron and that the diameter of the adjacent corner vessels is slightly larger but <6 micron.

Animals↗

PubMed2003

Red blood cell velocity and oxygen tension measurement in cerebral microvessels by double-wavelength photoexcitation.

Because the regulation of microcirculation in the cerebral cortex cannot be analyzed without measuring the blood flow dynamics and oxygen concentration in cerebral microvessels, we developed a fluorescence and phosphorescence system for estimating red blood cell velocity and oxygen tension in cerebral microcirculation noninvasively and continuously with high spatial resolution. Using red blood cells labeled with fluorescent isothiocyanate to visualize red cell distribution and using the oxygen quenching of Pd-meso-tetra-(4-carboxyphenyl)-porphyrin phosphorescence to measure oxygen tension enabled simultaneous measurement of blood velocity and oxygen tension. We examined how the measurement accuracy was affected by the spatial resolution and by the excitation laser light passing through the targeted microvessel and exciting the oxygen probe dye in the tissue beneath it. Focusing the excitation light into the microvessel stabilized the phosphorescence lifetime at each spatial resolution; moreover, it greatly reduced phosphorescence from the brain tissue. Animal experiments involving acute hemorrhagic shock demonstrated the feasibility of our system by showing that the changes in venular velocity and oxygen tension are synchronized to the change in mean arterial pressure. Our system measures the red cell velocity and oxygen concentration in the cerebral microcirculation by using the differences in luminescence and wavelength between fluorescence and phosphorescence, making it possible to easily acquire information about cerebral microcirculatory distribution and oxygen tension simultaneously.

Animals↗

PubMed2004

Lack of microvessels in well-differentiated regions of human head and neck squamous cell carcinoma A253 associated with functional magnetic resonance imaging detectable hypoxia, limited drug delivery, and resistance to irinotecan therapy.

PURPOSE: Combination chemotherapy with irinotecan (CPT-11; 50 mg/kg/week x 4 intravenously), followed 24 hour later by 5-fluorouracil (50 mg/kg/week x 4 intravenously), results in 10 and 100% cure rates of animals bearing human head and neck squamous cell carcinoma xenografts A253 and FaDu, respectively. A253 consists of 30% well-differentiated and avascular and 70% poorly differentiated regions with low microvessel density (10/x400), whereas FaDu is uniformly poorly differentiated with higher microvessel density (19/x400). Studies were carried out for determining the role of well-differentiated and avascular regions in drug resistance in A253 and detection of such regions with noninvasive functional magnetic resonance (fMR) imaging. EXPERIMENTAL DESIGN: Tumors were harvested for histopathologic evaluation and immunohistochemistry (CD31, CD34; differentiation marker: involucrin; hypoxia markers: carbonic anhydrase IX, pimonidazole; vascular endothelial factor (VEGF) and Ki67) immediately after fMR imaging following the 3rd dose of chemotherapy. High-performance liquid chromatography determination of intratumoral drug concentration of 7-ethyl-10-hydroxyl-camptothecin and autoradiography with (14)C-labeled CPT-11 was done 2 hours after CPT-11 administration. RESULTS: Although A253 xenografts showed three times higher concentration of 7-ethyl-10-hydroxyl-camptothecin, FaDu was more responsive to therapy. After therapy, A253 tumor consisted mostly (approximately 80%) of well-differentiated regions (positive for involucrin) lacking microvessels with a hypoxic rim (positive for carbonic anhydrase IX and pimonidazole) containing few proliferating (Ki67 positive) poorly differentiated cells. Autoradiography revealed that well-differentiated A253 tumor regions showed 5-fold lower (14)C-labeled CPT-11 concentrations compared with poorly differentiated areas (P < 0.001). Blood oxygen level dependant fMR imaging was able to noninvasively distinguish the hypoxic and well-vascularized regions within the tumors. CONCLUSION: Avascular-differentiated regions in squamous cell carcinoma offer sanctuary to some hypoxic but viable tumor cells (carbonic anhydrase IX and Ki67 positive) that escape therapy because of limited drug delivery. This study provides direct evidence that because of a specific histologic structure, avascular, well-differentiated hypoxic regions in tumors exhibit low drug uptake and represent a unique form of drug resistance.

Animals↗

PubMed1999

Successful autotransplantation of microvessel fragments into the rat heart.

We examined whether microvessel fragments (Mvf), autologously transplanted with myofibroblasts (Mf) into the heart, could survive and form connections to the host's coronary microcirculation. Neither achievement has been reported before in the heart. Mvf and Mf were prepared from Sprague-Dawley rat epididymal fat pads. A mixture of Mvf (labeled with the fluorescent probe DiI-acetylated low-density lipoprotein, DiI-Ac-LDL) and Mf was injected into the superficial myocardium under general anesthesia. Rats (n = 5 in each group) were killed on postoperative days 7, 14, 21, 42 and 49, and India ink was perfused through the coronary arteries. Frozen sections of the injected area were examined under fluorescence and light microscopes. Some DiI-Ac-LDL-labeled Mvf survived in each group, and India ink was present in the lumina of microvessels coincident with DiI-Ac-LDL-labeled autotransplanted Mvf. Hematoxylin and eosin staining revealed mild inflammatory reactions followed by some fibrosis at the injection sites. These findings indicate that autotransplanted Mvf can survive for at least 49 days, and that patent microvascular anastomoses can form between them and the host's coronary microvessels. Possibly, autotransplantation of Mvf could lead to the development of a new collateral microcirculation, a phenomenon especially important in the ischemic heart.

Animals↗

PubMedDate not supplied

Interactions between sensory perivascular nerves and the endothelium in brain microvessels.

The purpose of our study was to see if selective denervation of sensory perivascular nerves leads to changes in release of vasoactive substances of endothelial origin from brain microvessels during increased flow. Male rats pups were treated with the neurotoxin, capsaicin, to destroy primary afferent sensory nerves. Three months later, brain microvessels were isolated, placed on a micropore filter and perfused with Krebs buffer. During the course of a 30-min experiment, the flow rate was increased from 0.5 to 3.0 ml/min for two 3-min periods. The levels of ATP, substance P, vasopressin and endothelin in the effluent were measured. Microvessels from 5 rats were pooled for each perfusion experiment. Data from 5 perfusion experiments showed that the release of substance P was significantly higher in the capsaicin-treated rats during the second period of increased flow (3.02 +/- 1.04 pmol/min/mg protein) compared to the vehicle-treated controls (0.30 +/- 0.21 pmol/min/mg protein; p < 0.02). In contrast, the release of ATP at low flow and during the second period of increased flow was significantly lower in the capsaicin-treated rats (0.21 +/- 0.04 compared to 0.50 +/- 0.03 pmol/min/mg protein for controls at low flow, p < 0.001; and 1.19 +/- 0.15 compared to 2.11 +/- 0.26 pmol/min/mg protein for controls during the second period of increased flow, p < 0.01). The release patterns of endothelin and vasopressin were similar in capsaicin-treated and vehicle-treated controls. In conclusion, chronic depletion of sensory innervation leads to altered release of two endothelium-dependent vasodilators, ATP and substance P from the brain microvasculature.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗