共查询到20条相似文献,搜索用时 15 毫秒
1.
Borge BA Iversen VV Reed RK 《American journal of physiology. Heart and circulatory physiology》2006,290(5):H2108-H2115
Docetaxel and prostaglandin E1 (PGE1) increase transcapillary albumin extravasation and reduce interstitial fluid pressure in the skin. In this study the microdialysate concentration (Cm) of 125I-labeled human serum albumin (125I-HSA) and different-sized endogenous plasma proteins (EPP) was compared to evaluate changes in transcapillary extravasation of plasma proteins. 125I-HSA was also used to estimate changes in the specific activity of albumin. Extravasation of 125I-HSA and EPP from plasma to interstitium in the rat skin was compared during continuous administration of docetaxel and PGE1 by using microdialysis in anesthetized rats. Also, 20 ml of Ringer solution (RS) were injected intravenously during 10 min in a separate group. Two hollow plasmapheresis fibers (3 cm, cut off 3,000 kDa), one acting as control, were placed subcutaneously on the back skin and perfused with RS (5 microl/min, 140 min, collected every 10 min). The size of the different EPP was estimated to be 73, 65, 56, 47, and 39 A, separated by a size-exclusion high-performance liquid chromatography column and quantified by UV detection (280 nm). Docetaxel (0.5 mg/ml, n = 5) increased Cm of 125I-HSA and EPP of sizes 73, 65, 56, and 39 A significantly (P < 0.05) compared with control. PGE1 (20 microg/ml, n = 6) increased Cm of 125I-HSA significantly (P < 0.05) but none of the different-sized EPP was increased compared with control. Intravenous RS (20 ml, n = 6) increased Cm of 125I-HSA and increased all the different-sized EPP significantly (P < 0.05) compared with control. Although the microdialysis method is able to monitor qualitative changes in capillary permeability, a quantitative determination of the capillary reflection coefficient or permeability-surface area product was not possible, because steady state between plasma and dialysate was not achieved during the measurement period. The different pattern of extravasation of EPP and 125I-HSA after docetaxel, PGE1, and RS indicates increased interstitial transport rate and/or increased capillary permeability after docetaxel and RS, whereas PGE1 seems to increase transcapillary fluid flux without altering the permeability. 相似文献
2.
Karlsen TV Iversen VV Forsberg E Kjellén L Reed RK Gjerde EA 《American journal of physiology. Heart and circulatory physiology》2004,286(3):H884-H888
Mast cell activation, or neurogenic inflammation, is known to induce lowering of interstitial fluid pressure (P(if)) and plasma protein extravasation (PPE) in several tissues from both rats and mice. To examine a possible role of connective tissue mast cells (CTMCs) in these inflammatory responses, we used mice with dysfunctional CTMCs due to lack of the N-deacetylase/N-sulfotransferase-2 enzyme (NDST-2(-/-)). P(if) and PPE were measured after challenge with compound 48/80 (C48/80), and P(if) alone was measured after treatment either with capsaicin, substance P (SP), or calcitonin gene-related peptide (CGRP). Measurements of P(if) in anesthetized (fentanyl/fluanison and midazolam, 1:1) mice were performed in paw skin with glass capillaries connected to a servo-controlled counterpressure system. PPE was measured with microdialysis by using hollow plasmapheresis fibers (cutoff at 3,000 kDa) placed subcutaneously on the back. Intravenous administration of C48/80 lowered P(if) significantly (P < 0.05) in NDST-2(-/-) mice (-1.67 +/- 0.42 mmHg) compared with vehicle (-0.57 +/- 0.17 mmHg) but the lowering was significantly (P < 0.05) less compared with that of the NDST-2(+/+) mice (-2.31 +/- 0.47 mmHg). PPE was increased 300% after treatment with C48/80 in NDST-2(+/+) mice, whereas there was no increase in PPE in NDST-2(-/-) mice. Capsaicin, SP, and CGRP lowered P(if) significantly (P < 0.05) compared with vehicle and to the same extent in both NDST-2(+/+) and NDST-2(-/-) mice. We can conclude that although NDST-2(-/-) mice demonstrate an altered response in P(if) after mast cell activation, there was no similar alteration after neurogenic inflammation. Therefore, we suggest that neurogenic inflammation in mouse skin is not exclusively dependent on intact CTMCs. 相似文献
3.
A luteotropic role for prostaglandins (PGs) during the luteal phase of the menstrual cycle of rhesus monkeys was suggested by the observation that intraluteal infusion of a PG synthesis inhibitor caused premature luteolysis. This study was designed to identify PGs that promote luteal function in primates. First, the effects of various PGs on progesterone (P) production by macaque luteal cells were examined in vitro. Collagenase-dispersed luteal cells from midluteal phase of the menstrual cycle (Day 6-7 after the estimated surge of LH, n = 3) were incubated with 0-5,000 ng/ml PGE2, PGD, 6 beta PGI1 (a stable analogue of PGI2), PGA2, or PGF2 alpha alone or with hCG (100 ng/ml). PGE2, PGD2, and 6 beta PGI1 alone stimulated (p less than 0.05) P production to a similar extent (2- to 3-fold over basal) as hCG alone, whereas PGA2 and PGF2 alpha alone had no effect on P production. Stimulation (p less than 0.05) of P synthesis by PGE2, PGD2, and 6 beta PGI1 in combination with hCG was similar to that of hCG alone. Whereas PGA2 inhibited gonadotropin-induced P production (p less than 0.05), that in the presence of PGF2 alpha plus hCG tended (p = 0.05) to remain elevated. Second, the effects of various PGs on P production during chronic infusion into the CL were studied in vivo. Saline with or without 0.1% BSA (n = 12), PGE2 (300 ng/h; n = 4), PGD2 (300 ng/h; n = 4), 6 beta PGI1 (500 ng/h; n = 3), PGA2 (300 ng/h; n = 4), or PGF2 alpha (10 ng/h; n = 8) was infused via osmotic minipump beginning at midluteal phase (Days 5-8 after the estimated LH surge) until menses. In addition, the same dose of PGE, PGD, PGI, or PGA was infused in combination with PGF2 alpha (n = 3-4/group) for 7 days. P levels over 5 days preceding treatment were not different among groups. In 5 of 8 monkeys receiving PGF2 alpha alone, P declined to less than 0.5 ng/ml within 72 h after initiation of infusion and was lower (p less than 0.05) than controls. The length of the luteal phase in PGF2 alpha-infused monkeys was shortened (12.3 +/- 0.9 days; mean +/- SEM, n = 8; p less than 0.05) compared to controls (15.8 +/- 0.5). Intraluteal infusion of PGE, PGD, PGI, or PGA alone did not affect patterns of circulating P or luteal phase length.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
4.
Mullick AE Zaid UB Athanassious CN Lentz SR Rutledge JC Symons JD 《American journal of physiology. Regulatory, integrative and comparative physiology》2006,291(5):R1349-R1354
We have reported that hyperhomocysteinemia (HHcy) evoked by folate depletion increases arterial permeability and stiffness in rats and that low folate without HHcy increases arterial permeability in mice. In this study, we hypothesized that HHcy independently increases arterial permeability and stiffness in mice. C57BL/6J mice that received rodent chow and water [control (Con), n=12] or water supplemented with 0.5% L-methionine (HHcy, n=12) for 18+/-3 wk had plasma homocysteine concentrations of 8+/-1 and 41+/-1 microM, respectively (P<0.05), and similar liver folate (approximately 12+/-2 microg folate/g liver). Carotid arterial permeability, assessed as dextran accumulation using quantitative fluorescence microscopy, was greater in HHcy (3.95+/-0.4 ng.min-1.cm-2) versus Con (2.87+/-0.41 ng.min-1.cm-2) mice (P<0.05). Stress versus strain curves generated using an elastigraph indicated that 1) maximal stress (N/mm2), 2) physiological stiffness (low-strain Young's modulus, mN/mm), and 3) maximal stiffness (high-strain Young's modulus, N/mm) were higher (P<0.05) in aortas from HHcy versus Con mice. Thus, chronic HHcy increases arterial permeability and stiffness. Carotid arterial permeability also was assessed in age-matched C57BL/6J mice before and after incubation with 1) xanthine (0.4 mg/ml)/xanthine oxidase (0.2 mg/ml; X/XO) to generate superoxide anion (O2-) or 50 microM DL-homocysteine in the presence of 2) vehicle, 3) 300 microM diethylamine-NONOate (DEANO; a nitric oxide donor), or 4) 10(-3) M 4,5-dihydroxy-1,3-benzene disulfonic acid (tiron; a nonenzymatic intracellular O2- scavenger). Compared with preincubation values, X/XO and dl-homocysteine increased (P<0.05) permeability by 66+/-11% and 123+/-8%, respectively. DL-Homocysteine-induced increases in dextran accumulation were blunted (P<0.05) by simultaneous incubation with DEANO or tiron. Thus, acute HHcy increases arterial permeability by generating O2- to an extent whereby nitric oxide bioavailability is reduced. 相似文献
5.
Vasodilating actions of Ginkgo biloba extract (GBE) and bilobalide, a main constituent, were examined using rat aorta ring strips. GBE at the concentration ranges from 0.03 to 3 mg/ml had a potent concentration-dependent relaxation, reaching 70 +/- 4.5% (n = 6, P < 0.001) at 3 mg/ml. Bilobalide at 0.1 to 100 microM also caused the relaxation in a concentration-dependent manner. At 100 microM, bilobalide caused dilation by 17.6 +/- 3.9% (n = 7, P < 0.05). NG-monomethyl-L-arginine acetate (L-NMMA)(100 microM), an NO synthesis inhibitor, reduced the vasodilation of GBE (3 mg/ml) to 57.6 +/- 2.5% (n = 6, P < 0.05), and was accompanied with a decrease in the rate of relaxation. Tetraethylammonium (TEA)(100 microM), a Ca(2+)-activated K(+) channel inhibitor, also decreased the GBE (3 mg/ml)-induced relaxation to 63.1 +/- 4.6% (n = 6), but not significantly. Indomethacin tended to reduce the GBE (3 mg/ml)-induced vasorelaxation to 67.3 +/- 4.1% (n = 6). In contrast, the vasorelaxation of GBE (3 mg/ml) was strongly attenuated to 53 +/- 6.1% (n = 7, P < 0.05) in Ca(2+)-free medium. Similarly, the vasorelaxation induced by bilobalide significantly decreased both by pretreatment with NO inhibitor (L-NMMA) and in Ca(2+)-free solution. These results indicate that the relaxation induced by GBE would be due to the inhibition of Ca(2+) influx through the Ca(2+) channel and the activation of NO release, and might be in part due to the inhibitions of Ca(2+)-activated K(+) current and PGI(2) release, in the endothelium and aortic vascular muscles. Bilobalide possesses the similar mechanisms for the vasodilation. 相似文献
6.
Kawasaki F Matsuda M Kanda Y Inoue H Kaku K 《American journal of physiology. Endocrinology and metabolism》2005,288(3):E510-E518
To evaluate preventive effects of pioglitazone on pancreatic beta-cell damage in C57BL/KsJ db/db mice, an obese diabetic animal model, the pancreatic islets were compared morphologically between pioglitazone-treated (100 mg/kg daily po) and untreated db/db mice (n = 7 for each) after a 12-wk intervention (6-18 wk of age). The fasting blood glucose level was significantly improved by the treatment with pioglitazone (260 +/- 12 vs. 554 +/- 62 mg/dl, P < 0.05). The islet mass in the pancreas was significantly greater in pioglitazone-treated mice than in untreated mice (10.2 +/- 1.1 vs. 4.6 +/- 0.2 mg, P < 0.01). Subsequently, biochemical and physiological analyses of the beta-cell function were employed using pioglitazone-treated and untreated db/db mice (n = 6 for each) and pioglitazone-treated and untreated db/+ mice (n = 6 for each). After 2 wk of treatment (10-12 wk of age), the plasma levels of triglyceride and free fatty acid were significantly decreased, whereas the plasma adiponectin level increased significantly compared with the untreated group (65.2 +/- 18.0 vs. 18.3 +/- 1.3 microg/ml, P < 0.05). Pioglitazone significantly reduced the triglyceride content in the islets (43.3 +/- 3.6 vs. 65.6 +/- 7.6 ng/islet, P < 0.05) with improved glucose-stimulated insulin secretion. Pioglitazone showed no significant effects on the biochemical and physiological parameters in db/+ mice. The present study first demonstrated that pioglitazone prevents beta-cell damage in an early stage of the disease progression in db/db mice morphologically and physiologically. Our results suggest that pioglitazone improves glucolipotoxicity by increasing insulin sensitivity and reducing fat accumulation in the pancreatic islets. 相似文献
7.
Jaroszewski JJ Skarzynski DJ Hansel W 《Experimental biology and medicine (Maywood, N.J.)》2003,228(9):1057-1062
To test whether nitric oxide (NO) is involved in prostaglandin (PG) F2alpha-induced regression of the bovine corpus luteum (CL) in vivo, heifers were treated as follows: Group 1, saline (3 ml/h); Group 2, dinoprost, an analogue of prostaglandin F2alpha (aPGF2alpha; 5 mg/0.5 h); Group III, Nomega-nitro-L-arginine methyl ester (L-NAME; 200 mg/4 h), an inhibitor of nitric oxide synthase; and Group IV, L-NAME (400 mg/4 h) and aPGF2alpha (5 mg/0.5 h). All treatments were administered by an intraluteal microdialysis system (MDS) on day 15 of the cycle. Perfusate and jugular plasma samples were collected at half-hour intervals; additionally, jugular plasma samples were collected once daily from day 16 to day 21 of the cycle. In the perfusate samples, aPGF2alpha increased P4 (P < 0.05), PGE2 (P < 0.001), and LTC4 (P < 0.05) concentrations; L-NAME increased P4 (P < 0.05) but did not change PGE2 and LTC4 (P > 0.05) concentrations as compared with the period before treatment. Simultaneous perfusion of CL with L-NAME and aPGF2alpha caused a further increase of P4 concentration (P < 0.05) induced by L-NAME or aPGF2alpha treatment and increased PGE2 and LTC4 (P < 0.001) concentrations to the level observed after aPGF2alpha treatment. Perfusion of CL with aPGF2alpha caused luteal regression within 24 h, while perfusion with L-NAME prolonged the life span of CL to day 21 (P < 0.05). Concomitant L-NAME and aPGF2alpha treatment partially counteracted (P < 0.05) the luteal regression caused by aPGF2alpha administration. These results show that NO is involved in the process of luteolysis in the bovine CL and suggest that the luteolytic effect of aPGF2alpha may be mediated by NO as an important component of an autocrine/paracrine luteolytic cascade. 相似文献
8.
Tolnai J Szabari MV Albu G Maár BA Parameswaran H Bartolák-Suki E Suki B Hantos Z 《Journal of applied physiology (Bethesda, Md. : 1985)》2012,112(11):1932-1939
The aim of this study was to evaluate airway structure-function relations in elastase-induced emphysema in rats. Sprague-Dawley rats were treated intratracheally with 50 IU porcine pancreatic elastase (PPE, n = 8) or saline (controls, n = 6). Six weeks later, lung volumes [functional residual capacity (FRC), residual volume (RV), and total lung capacity (TLC)] and low-frequency impedance parameters (Newtonian resistance, R(N); tissue damping; tissue elastance, H) were measured, and tracheal sounds were recorded during slow inflation to TLC following in vivo degassing. The lungs were fixed and stained for standard morphometry, elastin, and collagen. In the PPE group, FRC and RV were higher [4.53 ± 0.7 (SD) vs. 3.28 ± 0.45 ml; P = 0.003 and 1.06 ± 0.35 vs. 0.69 ± 0.18 ml; P = 0.036, respectively], and H was smaller in the PPE-treated rats than in the controls (1,344 ± 216 vs. 2,178 ± 305 cmH(2)O/l; P < 0.001), whereas there was no difference in R(N). The average number of crackles per inflation was similar in the two groups; however, the crackle size distributions were different and the lower knee of the pressure-volume curves was higher in the PPE group. Microscopic images revealed different alveolar size distributions but similar bronchial diameters in the two groups. The treatment caused a slight but significant decrease in the numbers of alveolar attachments, no difference in elastin and slightly increased mean level and heterogeneity of collagen in the bronchial walls. These results suggest that tissue destruction did not affect the conventionally assessed airway resistance in this emphysema model, whereas the alterations in the recruitment dynamics can be an early manifestation of impaired airway function. 相似文献
9.
Satoru Ito Edward P Ingenito Kelly K Brewer Lauren D Black Harikrishnan Parameswaran Kenneth R Lutchen Béla Suki 《Journal of applied physiology》2005,98(2):503-511
Enlargement of the respiratory air spaces is associated with the breakdown and reorganization of the connective tissue fiber network during the development of pulmonary emphysema. In this study, a mouse (C57BL/6) model of emphysema was developed by direct instillation of 1.2 IU of porcine pancreatic elastase (PPE) and compared with control mice treated with saline. The PPE treatment caused 95% alveolar enlargement (P = 0.001) associated with a 29% lower elastance along the quasi-static pressure-volume curves (P < 0.001). Respiratory mechanics were measured at several positive end-expiratory pressures in the closed-chest condition. The dynamic tissue elastance was 19% lower (P < 0.001), hysteresivity was 9% higher (P < 0.05), and harmonic distortion, a measure of collagen-related dynamic nonlinearity, was 33% higher in the PPE-treated group (P < 0.001). Whole lung hydroxyproline content, which represents the total collagen content, was 48% higher (P < 0.01), and alpha-elastin content was 13% lower (P = 0.16) in the PPE-treated group. There was no significant difference in airway resistance (P = 0.7). The failure stress at which isolated parenchymal tissues break during stretching was 40% lower in the PPE-treated mice (P = 0.002). These findings suggest that, after elastolytic injury, abnormal collagen remodeling may play a significant role in all aspects of lung functional changes and mechanical forces, leading to progressive emphysema. 相似文献
10.
Wei CC Lucchesi PA Tallaj J Bradley WE Powell PC Dell'Italia LJ 《American journal of physiology. Heart and circulatory physiology》2003,285(2):H784-H792
In the current study, interstitial fluid (ISF), bradykinin (BK), and angiotensin II (ANG II) levels were measured using cardiac microdialysis in conscious, nonsedated rats at baseline and at 48 h and 5 days after each of the following: sham surgery (sham, n = 6), sham + administration of ANG-converting enzyme inhibitor ramipril (R, n = 6), creation of aortocaval fistula (ACF, n = 6), ACF + R (n = 6), and ACF + R + BK2 receptor antagonist (HOE-140) administration (n = 6). At 5 days, both ISF ANG II and BK increased in ACF rats (P < 0.05); however, in ACF + R rats, ISF ANG II did not differ from basal levels and ISF BK increased greater than threefold above baseline at 2 and 5 days (P < 0.05). Five days after ACF, the left ventricular (LV) weight-to-body weight ratio increased 30% (P < 0.05) in ACF but did not differ from sham in ACF + R and ACF + R + HOE-140 rats despite similar systemic arterial pressures across all ACF groups. However, ACF + R + HOE-140 rats had greater postmortem wall thickness-to-diameter ratio and smaller cross-sectional diameter compared with ACF + R rats. There was a significant increase in mast cell density in ACF and ACF + R rats that decreased below sham in ACF + R + HOE-140 rats. These results suggest a potentially important interaction of mast cells and BK in the cardiac interstitium that modulates the pattern of LV remodeling in the acute phase of volume overload. 相似文献
11.
McCord JL Hayes SG Kaufman MP 《American journal of physiology. Heart and circulatory physiology》2008,295(5):H2043-H2045
Pyridoxal-phosphate-6-azophenyl-2'-4-disulfonate (PPADS), a purinergic 2 (P2) receptor antagonist, has been shown to attenuate the exercise pressor reflex in cats. In vitro, however, PPADS has been shown to block the production of prostaglandins, some of which play a role in evoking the exercise pressor reflex. Thus the possibility exists that PPADS blocks the exercise pressor reflex through a reduction in prostaglandin synthesis rather than through the blockade of P2 receptors. Using microdialysis, we collected interstitial fluid from skeletal muscle to determine prostaglandin E2 (PGE2) concentrations during the intermittent contraction of the triceps surae muscle before and after a popliteal arterial injection of PPADS (10 mg/kg). We found that the PGE2 concentration increased in response to the intermittent contraction before and after the injection of PPADS (both, P < 0.05). PPADS reduced the pressor response to exercise (P < 0.05) but had no effect on the magnitude of PGE2 production during contraction (P = 0.48). These experiments demonstrate that PPADS does not block the exercise pressor reflex through a reduction in PGE2 synthesis. We suggest that PGE2 and P2 receptors play independent roles in stimulating the exercise pressor reflex. 相似文献
12.
Dextran restores albumin-inhibited surface activity of pulmonary surfactant extract. 总被引:3,自引:0,他引:3
T Kobayashi K Ohta K Tashiro K Nishizuka W M Chen S Ohmura K Yamamoto 《Journal of applied physiology》1999,86(6):1778-1784
We examined the effect of dextran (molecular weight 71,000) in counteracting the surfactant inhibitory action of plasma albumin. The surface adsorption time of 0.5 mg/ml modified natural surfactant (MNS; porcine lung extract consisting of phospholipids and hydrophobic surfactant proteins) with 7.5 mg/ml albumin decreased from 681 to 143 s by addition of dextran at a concentration of 10 mg/ml (P < 0.01). The minimum surface tension of 2.0 mg/ml MNS with 30 mg/ml albumin decreased from over 21 mN/m to below 3 mN/m when dextran was added at a concentration of 10 mg/ml (P < 0.01). Surfactant-deficient newborn rabbits given 10 ml/kg of a liquid containing 2.0 mg/ml MNS with 30 mg/ml albumin had a mean tidal volume =5 ml/kg after 5 min of mechanical ventilation, but, in those animals given the liquid containing 10 mg/ml dextran also, the volume was >13 ml/kg (P < 0.05). Although the underlying mechanism remains to be elucidated, we conclude that dextran restores the albumin-inhibited surface activity of MNS. 相似文献
13.
Bivona BJ Park S Harrison-Bernard LM 《American journal of physiology. Renal physiology》2011,300(3):F618-F625
Diabetic nephropathy is a major cause of end-stage renal disease worldwide. The current studies were performed to determine the later stages of the progression of renal disease in type II diabetic mice (BKS; db/db). Methodology was developed for determining glomerular filtration rate (GFR) in conscious, chronically instrumented mice using continuous intravenous infusion of FITC-labeled inulin to achieve a steady-state plasma inulin concentration. Obese diabetic mice exhibited increased GFR compared with control mice. GFR averaged 0.313 ± 0.018 and 0.278 ± 0.007 ml/min in 18-wk-old obese diabetic (n = 11) and control (n = 13) mice, respectively (P < 0.05). In 28-wk-old obese diabetic (n = 10) and control (n = 15) mice, GFR averaged 0.348 ± 0.030 and 0.279 ± 0.009 ml/min, respectively (P < 0.05). GFR expressed per gram BW was significantly reduced in 18- and 28-wk-old obese diabetic compared with control mice (5.9 ± 0.3 vs. 9.0 ± 0.3; 6.6 ± 0.6 vs. 7.8 ± 0.3 μl·min(-1)·g body wt(-1)), respectively (P < 0.05). However, older nonobese type II diabetic mice had significantly reduced GFR (0.179 ± 0.023 ml/min; n = 6) and elevated urinary albumin excretion (811 ± 127 μg/day) compared with obese diabetic and control mice (514 ± 54, 171 ± 18 μg/day), which are consistent with the advanced stages of renal disease. These studies suggest that hyperfiltration contributes to the progression of renal disease in type II diabetic mice. 相似文献
14.
Kristen A Mehl J Mark Davis Julie M Clements Franklin G Berger Maria M Pena James A Carson 《Journal of applied physiology》2005,98(6):2219-2225
Moderate-intensity treadmill running can alter male Apc(Min/+) mouse polyp formation. This purpose of this study was to examine whether exercise mode differentially affects Apc(Min/+) mouse intestinal polyp development in male and female mice. Male and female Apc(Min/+) mice were randomly assigned to control, treadmill (18 m/min; 60 min/day; 6 days/wk), or voluntary wheel running (24-h access) groups. Nine weeks of training decreased total intestinal polyps by 29% in male treadmill runners (66 +/- 9; P = 0.038) compared with male controls (93 +/- 7). The number of large polyps (>/=1-mm diameter) were also reduced by 38% in male treadmill runners (49 +/- 6; P = 0.005) compared with male controls (79 +/- 6). Treadmill running in female Apc(Min/+) mice and wheel running in both genders did not affect polyp number or size. Spleen weight decreased in male treadmill runners (91 +/- 9 mg; P = 0.011) and wheel runners (75 +/- 6 mg; P = 0.004) compared with controls (141 +/- 13 mg). Plasma IL-6 was reduced by 96% in male treadmill runners (1.2 +/- 0.6 pg/ml) and 78% in male wheel runners (6.6 +/- 3.3 pg/ml) compared with control mice (27.9 +/- 2.8 pg/ml; P < 0.05). Female mice responded similarly with an 86% decrease in plasma IL-6 with treadmill running (3.2 +/- 1.2 pg/ml) and 90% decrease with wheel running (2.9 +/- 2.0 pg/ml) compared with control mice (21.1 +/- 5.3 pg/ml; P < 0.05). The crypt depth-to-villus height ratio in the intestine, an indirect marker of intestinal inflammation, decreased by 21 (P = 0.024) and 24% (P = 0.029), respectively, in male and female treadmill runners but not wheel runners. Physical activity-induced attenuation of intestinal polyp number and size is dependent on exercise mode and differs between genders. The modulation of systemic and intestinal inflammation may also depend on exercise mode. 相似文献
15.
Effect of cyclosporine, a P-glycoprotein inhibitor, on the pharmacokinetics of cefepime in rat blood and brain: a microdialysis study. 总被引:2,自引:0,他引:2
In clinical application, cefepime and cyclosporine are regularly combined in the treatment of organ transplant patients, so the interaction of these two drugs can be hypothesized. Therefore, the pharmacokinetics of cefepime alone and in combination with cyclosporine in rat using microdialysis coupled with HPLC-UV on-line system was evaluated in the study. Cefepime at three doses (20, 50, and 100 mg/kg) showed linear kinetics. After addition of cyclosporine, the mean residence time was increased from 34.9 min to 48.6 min (p<0.05, n=6), and the area under the concentration versus time curve (AUC) increased from 4775 min microg/ml to 6960 min microg/ml (p<0.01, n=6). While in the brain, AUC increased from 64.3 min microg/ml to 110.2 min microg/ml. In summary, cyclosporine (20 mg/kg) could significantly alter the simultaneously administered cefepime (50 mg/kg) unbound drug pharmacokinetic parameters in both blood and brain. 相似文献
16.
Antigen challenge of sensitized rats increases airway responsiveness to methacholine 总被引:1,自引:0,他引:1
We measured airway responsiveness to methacholine (MCh) of highly inbred rats before and after six inhalational challenges with antigen. Ten Brown-Norway rats (130-216 g) that were actively sensitized to ovalbumin (OA) received six challenges with OA at 5-day intervals beginning 19 days after sensitization. An aerosol of OA (5% wt/vol) was inhaled for 1, 2, 5, and 10 min or until pulmonary resistance (RL) increased by at least 50%. Challenges with aerosolized MCh were performed immediately before and 14 days after sensitization, 2 days after the 3rd OA exposure, and 2, 7, 12, and 17 days after the 6th OA challenge. Four unsensitized rats underwent inhalational challenges with MCh over an equivalent time period. Responsiveness to MCh was calculated as the concentration of MCh required to increase RL to 200% of the control value (EC200RL). Seven out of 10 rats in the experimental group reacted to the first OA challenge with an immediate increase in RL of greater than 50% of control (range 70-550%). Three animals were unreactive to OA. Base-line EC200RL for all rats undergoing sensitization was 2.13 mg/ml (geometric mean), and it did not change significantly after sensitization (2.05 mg/ml). However, EC200RL of the rats that reacted to OA (n = 7) decreased significantly after 3 (1.11 mg/ml; P less than 0.005) and 6 OA exposures (0.96 mg/ml; P less than 0.005). The increase in responsiveness to inhaled MCh was present 17 days after the last OA exposure (EC200RL = 1.40 mg/ml; P less than 0.05). EC200RL of neither the unreactive sensitized rats (n = 3) nor the control rats (n = 4) changed after OA challenges.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
17.
Iain T. Cameron Rosemary Leask Rodney W. Kelly David T. Baird 《Prostaglandins & other lipid mediators》1987,34(1)
The effects of our four medical treatments have been assessed on menstrual blood loss (MBL) and endometrial prostaglandin (PG) concentrations in 30 women with objectively confirmed menorrhagia. Patients were randomly treated with danazol, 200mg daily (n=6), mefanamic acid, 500mg three times daily during menses (n=8), norethisterone, 5mg twice daily from day 15–25 of the cyle (n=8) or a progesterone-impregnated coil releasing 65ug progesterone daily (n=8). Endometrial biopsies were obtained in the mid-luteal phase before and after treatment in 23 cases, and assayed for PG content using radioimmunoassay. Treatment with norethisterone had no effect on either MBL or the concentration of PGs in the endometrium. MBL was significantly reduced after treatment with mefanamic acid (P=0.05, n=6) and the progesterone coil (P0.05, n=6), was reduced in each of 4 cases treated with danazol in whom endometrial biopsies were available. Although there was no consistent change in endometrial PG cocentrations in either the mefamic acid or danazol groups, the lower MBL after insertion of the progesterone coil was associated with a reduced endometrial content of PGE, PGF2α and “total” PG (6oxo PGF1α+PGE+PGE2α)−P=0.05. Wherease the cyclooxygenase inhibitor mefenamic acid is likely to exert its effect on endometrial PGs at the time of menstruation itself, the continous administration of progesterone throught the menstrual cycle could result in both an impairment in estrogen receptor generation leading to reduced estrogen-mediated cyclooxygenase activity, and an increase in endometrial PG metabolism. 相似文献
18.
Involvement of nitric oxide synthase in skeletal muscle adaptation to chronic overload. 总被引:1,自引:0,他引:1
The purpose of this study was to determine the necessity of nitric oxide (NO) for hypertrophy and fiber-type transition in overloaded (OL) skeletal muscle. Endogenous NO production was blocked by administering N(G)-nitro-L-arginine methyl ester (L-NAME; 0.75 mg/ml; approximately 100 mg x kg-1 x day-1) in drinking water. Thirty-eight female Sprague-Dawley rats (approximately 250 g) were randomly divided into four groups: control-nonoverloaded (Non-OL), control-OL, L-NAME-Non-OL, and L-NAME-OL. Chronic overload of the plantaris was induced bilaterally by surgical removal of the gastrocnemius and soleus. Rats in the Non-OL groups received sham surgeries. L-NAME treatment began 24 h before surgery and continued until the rats were killed 14 days postsurgery. Although OL induced hypertrophy in both control (+76%) and L-NAME (+39%) conditions (P < 0.05), mean plantaris-to-body mass ratio in the L-NAME-OL group was significantly lower (P < 0.05) than that in the control-OL group. Microphotometric analysis of histochemically determined fiber types revealed increases in cross-sectional area (P < 0.05) for all fiber types (types I, IIA, and IIB/X) in the OL plantaris from control rats, whereas L-NAME-OL rats exhibited increases only in type I and IIB/X fibers. SDS-PAGE analysis of myosin heavy chain (MHC) composition in the plantaris indicated a significant (P < 0.05) OL effect in the control rats. Specifically, the mean proportion of type I MHC increased 6% (P < 0.05), whereas the proportion of type IIb MHC decreased approximately 9% (P < 0.05). No significant OL effects on MHC profile were observed in the L-NAME rats. These data support a role of NO in overload-induced skeletal muscle hypertrophy and fiber-type transition. 相似文献
19.
Guo ZL Longhurst JC 《American journal of physiology. Heart and circulatory physiology》2000,278(3):H843-H852
A number of metabolites produced during abdominal ischemia can stimulate and/or sensitize visceral afferents. The precise mechanisms whereby these metabolites act are uncertain. Other studies have shown that the adenylate cyclase-cAMP system may be involved in the activation of sensory neurons. Therefore, we hypothesized that cAMP contributes to the activation of ischemically sensitive abdominal visceral afferents. Single-unit activity of abdominal visceral C fibers was recorded from the right thoracic sympathetic chain in anesthetized cats before and during 7 min of abdominal ischemia. Forty-six percent of ischemically sensitive C fibers responded to intra-arterial injection of 8-bromo-cAMP (0.35-1. 0 mg/kg), an analog of cAMP, with responses during ischemia increasing from 0.50 +/- 0.06 to 0.84 +/- 0.08 impulses/s (P < 0.05, n = 11 C fibers). Conversely, an inhibitor of adenylate cyclase, 2', 5'-dideoxyadenosine (DDA; 0.1 mg/kg iv), attenuated ischemia-induced increase in activity of afferents from 0.66 +/- 0.10 to 0.34 +/- 0. 09 impulses/s (P < 0.05; n = 8). Furthermore, whereas exogenous PGE(2) (3-4 microg/kg ia) augmented the ischemia-induced increase in activity of afferents (P < 0.05, n = 10), treatment with DDA (0.1 mg/kg iv) substantially reduced the increase in discharge activity of afferents during ischemia, which was augmented by PGE(2) (1.45 +/- 0.24 vs. 0.70 +/- 0.09 impulses/s, -DDA vs. +DDA; P < 0.05) in six fibers. A time control group (n = 4), however, demonstrated similar increases in the activity of afferents with repeated administration of PGE(2). These data suggest that cAMP contributes to the activation of abdominal visceral afferents during ischemia, particularly to the action of PGs on activation and/or sensitization of these endings. 相似文献
20.
A Motta A M Franchi A Faletti A L Gimeno M A Gimeno 《Prostaglandins, leukotrienes, and essential fatty acids》1992,47(2):139-142
We attempted to explore possible mechanism(s) subserving the influence of oxytocin (O) and of progesterone (P) in the isolated rat uterus studying the action of these hormones on: the synthesis and release of prostaglandins (PGs), the metabolism of labelled arachidonic acid and the uptake of Ca2+ by the tissue from ovariectomized animals. The experiments were done with uterine preparations isolated from spayed rats treated or not with P prior to sacrifice and afterward incubated or not with O 'in vitro'. While uterine strips from untreated spayed rat uterus exhibited a basal release into the incubating medium of approximately the same amounts of PGF2 alpha, and PGE2, the 'in vitro' addition of O (50 mU/ml) increased significantly (p < 0.05) the output of PGF2 alpha without changing the release of PGE2. In tissue from rats injected with P prior to sacrifice the output of PGF2 alpha rose significantly (p < 0.01) as it did after the addition of O to preparations obtained from spayed rats treated with P in comparison to findings in uteri from spayed rats but not in comparison to uteri from spayed rats treated with P alone. Moreover, the 'in vitro' addition of O (50 mU/ml) only increased the formation of PGF2 alpha (p < 0.05) and of 5-HETE (p < 0.05); nevertheless the administration of P to spayed rats diminished significantly (p < 0.05) the formation of 6-keto-PGF1 alpha from uteri, but increased that of PGF2 alpha (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献