Thromboxane A2 mediates increased pulmonary microvascular permeability after intestinal reperfusion

1997 ◽  
Vol 82 (2) ◽  
pp. 592-598 ◽  
Author(s):  
Richard H. Turnage ◽  
John L. Lanoue ◽  
Kevin M. Kadesky ◽  
Yan Meng ◽  
Stuart I. Myers
Keyword(s):  
Intestinal Ischemia ◽  
Thromboxane A2 ◽  
Microvascular Permeability ◽  
Sprague Dawley ◽  
Pulmonary Vasoconstriction ◽  
Sprague Dawley Rats ◽  
Pulmonary Arterial ◽  
Synthase Inhibitor ◽  
Krebs Buffer

Turnage, Richard H., John L. LaNoue, Kevin M. Kadesky, Yan Meng, and Stuart I. Myers. Thromboxane A2 mediates increased pulmonary microvascular permeability after intestinal reperfusion. J. Appl. Physiol. 82(2): 592–598, 1997.—This study examines the hypothesis that intestinal reperfusion (IR)-induced pulmonary thromboxane A2(TxA2) release increases local microvascular permeability and induces pulmonary vasoconstriction. Sprague-Dawley rats underwent 120 min of intestinal ischemia and 60 min of IR. Sham-operated animals (Sham) served as controls. After IR or Sham, the pulmonary vessels were cannulated, and the lungs were perfused in vitro with Krebs buffer. Microvascular permeability was quantitated by determining the filtration coefficient ( K f), and pulmonary arterial (Ppa), venous (Ppv), and capillary (Ppc) pressures were measured to calculate vascular resistance (Rt). After baseline measurements, imidazole (TxA2 synthase inhibitor) or SQ-29,548 (TxA2-receptor antagonist) was added to the perfusate; then K f, Ppa, Ppv, and Ppc were again measured. The K fof lungs from IR animals was four times greater than that of Sham ( P = 0.001), and Rt was 63% greater in the injured group ( P = 0.01). Pc of IR lungs was twice that of controls (5.4 ± 1.0 vs. 2.83 ± 0.3 mmHg, IR vs. Sham, respectively; P < 0.05). Imidazole or SQ-29,548 returned K fto baseline measurements ( P < 0.05) and reduced Rt by 23 and 17%, respectively ( P < 0.05). IR-induced increases in Pc were only slightly reduced by 500 μg/ml imidazole (14%; P = 0.05) but unaffected by lower doses of imidazole (5 or 50 μg/ml) or SQ-29,548. These data suggest that IR-induced pulmonary edema is caused by both increased microvascular permeability and increased hydrostatic pressure and that these changes are due, at least in part, to the ongoing release of TxA2.

17β-Estradiol modulates vasoconstriction induced by endothelin-1 following trauma-hemorrhage

2007 ◽  
Vol 292 (1) ◽  
pp. H245-H250 ◽  
Author(s):  
Zheng F. Ba ◽  
Ailing Lu ◽  
Tomoharu Shimizu ◽  
László Szalay ◽  
Martin G. Schwacha ◽  
...  
Keyword(s):  
Control Level ◽  
No Synthase ◽  
Sprague Dawley ◽  
Response Curves ◽  
Endothelin 1 ◽  
Sprague Dawley Rats ◽  
17Β Estradiol ◽  
Synthase Inhibitor

Although endothelin-1 (ET-1) induces vasoconstriction, it remains unknown whether 17β-estradiol (E2) treatment following trauma-hemorrhage alters these ET-1-induced vasoconstrictive effects. In addition, the role of the specific estrogen receptor (ER) subtypes (ER-α and ER-β) and the endothelium-localized downstream mechanisms of actions of E2 remain unclear. We hypothesized that E2 attenuates increased ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway. To study this, aortic rings were isolated from male Sprague-Dawley rats following trauma-hemorrhage with or without E2 treatment, and alterations in tension were determined in vitro. Dose-response curves to ET-1 were determined, and the vasoactive properties of E2, propylpyrazole triol (PPT, ER-α agonist), and diarylpropionitrile (DPN, ER-β agonist) were determined. The results showed that trauma-hemorrhage significantly increased ET-1-induced vasoconstriction; however, administration of E2 normalized ET-1-induced vasoconstriction in trauma-hemorrhage vessels to the sham-operated control level. The ER-β agonist DPN counteracted ET-1-induced vasoconstriction, whereas the ER-α agonist PPT was ineffective. Moreover, the vasorelaxing effects of E2 were not observed in endothelium-denuded aortic rings or by pretreatment of the rings with a nitric oxide (NO) synthase inhibitor. Cyclooxygenase inhibition with indomethacin had no effect on the action of E2. Thus, E2 administration attenuates ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway that is dependent on endothelium-derived NO synthesis.

Notoginsenoside R1 Attenuates Hypoxia and Hypercapnia-Induced Vasoconstriction in Isolated Rat Pulmonary Arterial Rings by Reducing the Expression of ERK

2014 ◽  
Vol 42 (04) ◽  
pp. 799-816 ◽  
Author(s):  
Yixiao Xu ◽  
Lina Lin ◽  
Lanlan Tang ◽  
Mengxiao Zheng ◽  
Yingchun Ma ◽  
...  
Keyword(s):  
Pulmonary Arteries ◽  
Panax Notoginseng ◽  
Underlying Mechanism ◽  
Sprague Dawley ◽  
Third Order ◽  
Pulmonary Vasoconstriction ◽  
Sprague Dawley Rats ◽  
Specific Objective ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a disease of the small pulmonary arteries characterized by increased vascular resistance. Pulmonary vasoconstriction has been proven to play a pivotal role in PAH. We have previously hypothesized that Panax notoginseng saponins (PNS) might attenuate hypoxia–hypercapnia-induced pulmonary vasoconstriction. The specific objective of the present study was to investigate the role of notoginsenoside R1, a main ingredient of PNS, in this process and the possible underlying mechanism. The third order pulmonary rings from the Sprague-Dawley rats were treated with different concentrations of notoginsenoside R1 (8, 40, and 100 mg/L, respectively) both before and during the conditions of hypercapnia and hypoxia. Contractile force changes in the rings were detected and the optimal concentration (8 mg/L) was selected. Furthermore, an ERK inhibitor, U0126, was applied to the rings. In addition, pulmonary arterial smooth muscle cells (PASMCs) were cultured under hypoxic and hypercapnic conditions, and notoginsenoside R1 was administered to detect the changes induced by ERK1/2. The results revealed biphasic vasoconstriction in rings under hypoxic and hypercapnic conditions. It is hypothesized that the observed attenuation of vasoconstriction and the production of vasodilation could have been induced by notoginsenoside R1. This effect was found to be significantly reinforced by U0126 (p < 0.05 or p < 0.01). ERK expression in the PASMCs under hypoxic and hypercapnic conditions was significantly activated (p < 0.05 or p < 0.01) and the observed activation was attenuated by notoginsenoside R1 (p < 0.05 or p < 0.01). Our findings strongly support the significant role of notoginsenoside R1 in the inhibition of hypoxia–hypercapnia-induced vasoconstriction by the ERK pathway.

Heart and lung alterations in neonatal rats exposed to CO or high altitude

1992 ◽  
Vol 73 (5) ◽  
pp. 1713-1719 ◽  
Author(s):  
D. G. Penney ◽  
A. Tucker ◽  
G. A. Bambach
Keyword(s):  
High Altitude ◽  
Barometric Pressure ◽  
Ambient Air ◽  
Sprague Dawley ◽  
Altitude Exposure ◽  
Sprague Dawley Rats ◽  
Fort Collins ◽  
Pulmonary Arterial ◽  
Group 2

We wished to determine whether cardiac changes produced by CO are related to the development of pulmonary hypertension and whether they are specific for CO or also occur with high-altitude exposure. Newborn male Sprague-Dawley rats were exposed to 500 ppm CO for 32 days (CO) at Detroit, MI or to 11,500-ft simulated altitude at Fort Collins, CO (barometric pressure 495 Torr; 11K); ambient air controls were maintained at Detroit (657 ft, 200 m; AIR) and at Fort Collins (5,000 ft, 1,524 m; 5K). Rats were maintained at Fort Collins after 34 days of age. Hematocrit was elevated to a greater extent in the CO than in the 11K group 2 days postexposure; however, no differences existed 40, 76, or 112 days postexposure. Right ventricle (RV) and left ventricle plus septum (LV + S) mass in CO rats were increased 38.0 and 37.4%, respectively, relative to the AIR group 2 days after CO exposure; RV and LV + S in the 11K group were increased 55.7 and 9.3%, respectively, relative to the 5K group. Cardiac hypertrophy declined in the CO and 11K groups postexposure but remained significant for the RV, reaching 20.7% above the AIR group (CO) and 29.7% above the 5K group (11K) at 145 days of age. By use of an in vitro preparation, pulmonary vascular resistance (PVR) and pulmonary arterial pressure were significantly increased immediately after altitude but not after CO exposure and remained elevated in adulthood after altitude exposure. PVR was correlated with hematocrit in altitude- but not in CO-exposed rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PKC activates BKCa channels in rat pulmonary arterial smooth muscle via cGMP-dependent protein kinase

2004 ◽  
Vol 286 (6) ◽  
pp. L1275-L1281 ◽  
Author(s):  
Scott A. Barman ◽  
Shu Zhu ◽  
Richard E. White
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Channel Activity ◽  
Sprague Dawley ◽  
Dependent Protein Kinase ◽  
Pulmonary Vasoconstriction ◽  
Sprague Dawley Rat ◽  
Dependent Protein ◽  
Pulmonary Arterial ◽  
Pulmonary Arterial Smooth Muscle

Normally, signaling mechanisms that activate large-conductance, calcium- and voltage-activated potassium (BKCa) channels in pulmonary vascular smooth muscle cause pulmonary vasodilatation. BKCa-channel modulation is important in the regulation of pulmonary arterial pressure, and inhibition (decrease in the opening probability) of the BKCa channel has been implicated in the development of pulmonary vasoconstriction. Protein kinase C (PKC) causes pulmonary vasoconstriction, but little is known about the effect of PKC on BKCa-channel activity in pulmonary vascular smooth muscle. Accordingly, studies were done to determine the effect of PKC on BKCa-channel activity using patch-clamp studies in pulmonary arterial smooth muscle cells (PASMCs) of the Sprague-Dawley rat. The PKC activators phorbol myristate acetate (PMA) and thymeleatoxin opened BKCa channels in single Sprague-Dawley rat PASMC. The activator response to both PMA and thymeleatoxin on BKCa-channel activity was blocked by Gö-6983, which selectively blocks PKC-α, -δ, -γ, and -ζ, and by rottlerin, which selectively inhibits PKC-δ. In addition, the specific cyclic GMP-dependent protein kinase antagonist KT-5823 blocked the responses to PMA and thymelatoxin, whereas the specific cyclic AMP-dependent protein kinase blocker KT-5720 had no effect. In isolated pulmonary arterial vessels, both PMA and forskolin caused vasodilatation, which was inhibited by KT-5823, Gö-6983, or the BKCa-channel blocker tetraethylammonium. The results of this study indicate that activation of specific PKC isozymes increases BKCa-channel activity in Sprague-Dawley rat PASMC via cyclic GMP-dependent protein kinase, which suggests a unique signaling mechanism for vasodilatation.

scholarly journals Pharmacological comparison of four biopolymeric natural gums as hemostatic agents for management of bleeding wounds: preliminary in vitro and in vivo results

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Himanshu Kushwah ◽  
Nidhi Sandal ◽  
Meenakshi Chauhan ◽  
Gaurav Mittal
Keyword(s):  
Xanthan Gum ◽  
Guar Gum ◽  
Human Lymphocytes ◽  
Sprague Dawley ◽  
Gum Tragacanth ◽  
Civilian Trauma ◽  
Sprague Dawley Rats ◽  
Cytotoxicity Studies

Abstract Background Uncontrolled bleeding is one of the primary reasons for preventable death in both civilian trauma and military battle field. This study evaluates in vitro and in vivo hemostatic potential of four biopolymeric natural gums, namely, gum tragacanth, guar gum, xanthan gum, and gum acacia. In vitro evaluation of whole blood clotting time and erythrocyte agglutination assay were carried out. In vitro cytotoxicity studies with respect to each gum were done in human lymphocytes to ascertain percent cell viability. In vivo hemostatic potential of each gum (as sponge dressing and powder form) was evaluated in Sprague Dawley rats using tail bleeding assay and compared with commercially available hemostatic sponge. Other important parameters like (a) time taken for complete hemostasis, (b) amount of blood absorbed, (c) adherence strength of developed hemostatic dressing(s), (d) incidence of re-bleeding, and (e) survival of animals were also studied. Results Of the four test gums studied, xanthan gum (@3mg/ml of blood) and gum tragacanth (@35mg/ml of blood) were able to clot blood in least time (58.75±6.408 s and 59.00±2.082 s, respectively) and exhibited very good hemostatic potential in vitro. Except for xanthan gum, all other test gums did not exhibit any significant cytotoxicity at different time points till 24 h. In rat tail bleeding experiments, gum tragacanth sponge dressing and powder achieved hemostasis in least time (156.2±12.86 s and 76±12.55 s, respectively) and much earlier than commercially available product (333.3±38.84 s; p˂0.01). Conclusion Results indicate potential of gum tragacanth to be developed into a suitable hemostatic product.

Bioavailability in Vivo of Benzo[a]Pyrene Adsorbed to Diesel Particulate

1991 ◽  
Vol 7 (3) ◽  
pp. 125-139 ◽  
Author(s):  
David R. Bevan ◽  
David M. Ruggio
Keyword(s):  
Health Risks ◽  
Quantitative Description ◽  
Intratracheal Instillation ◽  
Direct Analysis ◽  
Sprague Dawley ◽  
Reasonable Estimate ◽  
Diesel Particulate ◽  
Sprague Dawley Rats

To evaluate health risks associated with exposure to particulates in the environment, it is necessary to quantify the bioavailability of carcinogens associated with the particulates. Direct analysis of bioavailability in vivo is most readily accomplished by adsorbing a radiolabeled form of the carcinogen to the particulate. A sam ple of native diesel particulate collected from an Oldsmobile die sel engine that contained 1.03 μ g benzo[ a] pyrene ( BaP)/ g particulate was supplemented with exogenous [ 3 H]- BaP to pro duce a particulate containing 2.62 μ g BaP/g. To insure that elu tion of BaP from native and [3 H] -BaP-supplemented particulate was similar, in vitro analyses were performed. When using phos pholipid vesicles composed of dimyristoylphosphatidylcholine (DMPC), 1.52% of total BaP was eluted from native particulate into the vesicles in 18 hrs; from [ 3 H] -BaP supplemented particu late, 1.68% was eluted. Using toluene as eluent, 2.55% was eluted from native particulate, and 8.25% from supplemented particulate, in 6 hrs. Supplemented particulate was then instilled intratracheally into male Sprague-Dawley rats and distribution of radioactivity was analyzed at selected times over 3 days. About 50% of radioactivity remained in lungs at 3 days following instil lation, with 30% being excreted into feces and the remainder dis tributed throughout the organs of the rats. To estimate the amount of radioactivity that entered feces through swallowing of a portion of the instilled dose, [3 H] -BaP-supplemented particu late was instilled intratracheally into rats that had a cannula sur gically implanted in the bile duct. Rate of elimination of radio activity into bile was monitored; 10.6% of radioactivity was re covered in 6 hr, an amount slightly lower than the 12.8% ex creted in 6 hrs into feces of animals with intact bile ducts. Our studies provide a quantitative description of the distribution of BaP and its metabolites following intratracheal instillation of diesel particulate. Because rates of elution of BaP in vitro are similar for native diesel particulate and particulate with supple mental [ 3H] -BaP, our results provide a reasonable estimate of the bioavailability in vivo of BaP associated with diesel particu late.

Safety Assessment of a Hydroethanolic Extract of Caralluma fimbriata

2013 ◽  
Vol 32 (5) ◽  
pp. 385-394 ◽  
Author(s):  
Antoinette Y. Odendaal ◽  
Narendra S. Deshmukh ◽  
Tennille K. Marx ◽  
Alexander G. Schauss ◽  
John R. Endres ◽  
...  
Keyword(s):  
Developmental Toxicity ◽  
Toxicity Study ◽  
Developmental Study ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Toxicological Assessment ◽  
Sprague Dawley Rats ◽  
Chromosomal Aberration Test ◽  
Hydroethanolic Extract

This toxicological assessment evaluated the safety of a hydroethanolic extract prepared from Caralluma fimbriata (CFE), a dietary supplement marketed worldwide as an appetite suppressant. Studies included 2 in vitro genotoxicity assays, a repeated dose oral toxicity study, and a developmental study in rats. No evidence of in vitro mutagenicity or clastogenicity surfaced in the in vitro studies at concentrations up to 5000 μg of extract/plate (Ames test) or 5000 μg of extract/mL (chromosomal aberration test). No deaths or treatment-related toxicity were seen in the 6-month chronic oral toxicity study in Sprague-Dawley rats conducted at 3 doses (100, 300, and 1000 mg/kg body weight (bw)/d). The no observed effect level for CFE in this study was considered to be 1000 mg/kg bw/d. A prenatal developmental toxicity study conducted at 3 doses (250, 500, and 1000 mg/kg bw/d) in female Sprague-Dawley rats resulted in no treatment-related external, visceral, or skeletal fetal abnormalities, and no treatment-related maternal or pregnancy alterations were seen at and up to the maximum dose tested. CFE was not associated with any toxicity or adverse events.

Metabolism of triallate in Sprague-Dawley rats. 3. In vitro metabolic pathways

1993 ◽  
Vol 41 (1) ◽  
pp. 141-147 ◽  
Author(s):  
Amy G. Hackett ◽  
John J. Kotyk ◽  
Hideji. Fujiwara ◽  
Eugene W. Logusch
Keyword(s):  
Metabolic Pathways ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

scholarly journals Cholesterol induces renal vasoconstriction and anti-natriuresis by inhibiting nitric oxide production in anesthetized rats

2009 ◽  
Vol 297 (6) ◽  
pp. F1606-F1613 ◽  
Author(s):  
Libor Kopkan ◽  
Md Abdul H. Khan ◽  
Agnieszka Lis ◽  
Mouhamed S. Awayda ◽  
Dewan S. A. Majid
Keyword(s):  
Nitric Oxide ◽  
Sodium Reabsorption ◽  
No Production ◽  
Sprague Dawley ◽  
Appreciable Change ◽  
Renal Vasoconstriction ◽  
Sprague Dawley Rats ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor ◽  
Renal Responses

Although hypercholesterolemia is implicated in the pathophysiology of many renal disorders as well as hypertension, its direct actions in the kidney are not yet clearly understood. In the present study, we evaluated renal responses to administration of cholesterol (8 μg·min−1·100 g body wt−1; bound by polyethylene glycol) into the renal artery of anesthetized male Sprague-Dawley rats. Total renal blood flow (RBF) was measured by a Transonic flow probe, and glomerular filtration rate (GFR) was determined by Inulin clearance. In control rats ( n = 8), cholesterol induced reductions of 10 ± 2% in RBF [baseline (b) 7.6 ± 0.3 μg·min−1·100 g−1], 17 ± 3% in urine flow (b, 10.6 ± 0.9 μg·min−1·100 g−1), 29 ± 3% in sodium excretion (b, 0.96 ± 0.05 μmol·min−1·100 g−1) and 24 ± 2% in nitrite/nitrate excretion (b, 0.22 ± 0.01 nmol·min−1·100 g−1) without an appreciable change in GFR (b, 0.87 ± 0.03 ml·min−1·100 g−1). These renal vasoconstrictor and anti-natriuretic responses to cholesterol were absent in rats pretreated with nitric oxide (NO) synthase inhibitor, nitro-l-arginine methylester (0.5 μg·min−1·100 g−1; n = 6). In rats pretreated with superoxide (O2−) scavenger tempol (50 μg·min−1·100 g−1; n = 6), the cholesterol-induced renal responses remained mostly unchanged, although there was a slight attenuation in anti-natriuretic response. This anti-natriuretic response to cholesterol was abolished in furosemide-pretreated rats (0.3 μg·min−1·100 g−1; n = 6) but remained unchanged in amiloride-pretreated rats (0.2 μg·min−1·100 g−1; n = 5), indicating that Na+/K+/2Cl− cotransport is the dominant mediator of this effect. These data demonstrate that cholesterol-induced acute renal vasoconstrictor and antinatriuretic responses are mediated by a decrease in NO production. These data also indicate that tubular effect of cholesterol on sodium reabsorption is mediated by the furosemide sensitive Na+/K+/2Cl− cotransporter.

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