Effects of PAF on isolated rat airways perfused with blood-free solution

1991 ◽  
Vol 260 (4) ◽  
pp. L260-L267
Author(s):  
N. M. Munoz ◽  
C. F. Kirchhoff ◽  
M. E. Strek ◽  
R. N. Blumenthal ◽  
A. R. Leff
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Platelet Activating Factor ◽  
Tissue Perfusion ◽  
Sprague Dawley ◽  
Response Curves ◽  
Peripheral Airways ◽  
Sprague Dawley Rats ◽  
Lung Resistance ◽  
Prior Administration

We examined the mechanism of constriction and muscarinic augmentation of contraction of airway smooth muscle caused by platelet-activating factor (PAF) in airways from 55 Sprague-Dawley rats perfused through the isolated bronchial circulation (BC) and pulmonary circulation (PC) and isometrically in tissue perfusion chambers. Dose-response curves were generated cumulatively by infusing 10(-10) to 10(-7) mol PAF dissolved in Krebs-Henseleit solution buffer containing 4% bovine serum albumin into the BC or PC. The efficacy of PAF in central airways (BC) was approximately twofold greater in increasing lung resistance (RL) than for more peripheral airways perfused by the PC (P less than 0.05). Tachyphylaxis was demonstrated in both BC and PC for preparations in which a second PAF dose-response curve was generated. Bolus injection of 10(-6) mol of the PAF antagonist, CV-6209, plus 10(-7) mol PAF caused 81% reversal of the maximal BC response. The same dose of CV-6209 reversed the response to PAF in the PC by 99.2%. Initial administration of 10(-6) mol CV-6209 with PAF prevented completely contraction elicited by PAF in the BC and PC. Concentration-response studies also were generated isometrically in tissue perfusion chambers from 64 tracheal smooth muscle strips. Maximal contraction elicited by 10(-6) M PAF was blocked completely with 10(-6) M CV-6209. In separate studies, addition of 10(-6) mol CV-6209 to the BC perfusate caused 93% blockade of the RL response to PAF and 100% inhibition when administered in the PC. Prior administration of PAF caused two- to fourfold augmentation of the contractile response to acetylcholine (ACh) within the same preparation; in the presence of CV-6209, the response to ACh was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

PAF-induced contraction of canine trachea mediated by 5-hydroxytryptamine in vivo

1989 ◽  
Vol 66 (2) ◽  
pp. 638-643 ◽  
Author(s):  
T. M. Murphy ◽  
N. M. Munoz ◽  
J. Moss ◽  
J. S. Blake ◽  
M. M. Mack ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Contractile Response ◽  
Platelet Activating Factor ◽  
Smooth Muscle Contraction ◽  
Active Tension ◽  
Response Curves ◽  
Arteriovenous Difference

We studied the secretory correlates of tracheal smooth muscle contraction caused by platelet-activating factor (PAF) in nine mongrel dogs in vivo. In five dogs, dose-response curves were generated by rapid intra-arterial injection of 10(-10) to 10(-6) mol PAF into the isolated tracheal circulation; tracheal contractile response was measured isometrically in situ. To examine the mechanism by which PAF elicits contraction of canine trachealis, concentrations of serotonin (5-HT) and histamine were assayed in the venous effluent as the arteriovenous difference (AVd) in mediator concentration across the airway for each level of contraction. PAF caused dose-related active tracheal tension to a maximum of 37.2 +/- 5.4 g/cm (10(-6) mol PAF). The AVd in 5-HT increased linearly from 0.20 +/- 0.05 (10(-9) mol PAF) to 3.5 +/- 0.3 ng/ml (10(-6) mol PAF) (P less than 0.005). In contrast, the AVd in histamine was insignificant and did not change with increasing doses of PAF. A positive correlation was obtained between the AVd in 5-HT and active tracheal tension (r = 0.92, P less than 0.001); there was no correlation between AVd in histamine and active tension (r = -0.16). PAF-induced parasympathetic activation was not mediated by 5-HT; contraction elicited by exogenous 5-HT was not affected by muscarinic blockade. We conclude that nonparasympathetically mediated contraction elicited acutely by PAF in dogs results at least in part from secondary release of serotonin and is not mediated by histamine.

Site of methacholine reactivity in the peripheral airways: analysis using lung explants

1997 ◽  
Vol 272 (1) ◽  
pp. L68-L72 ◽  
Author(s):  
J. L. Wright ◽  
J. P. Sun ◽  
A. Churg
Keyword(s):  
Smooth Muscle ◽  
Airway Responsiveness ◽  
Sprague Dawley ◽  
Peripheral Airways ◽  
Sprague Dawley Rats ◽  
Airway Response ◽  
Rule Out

We used a recently developed lung explant technique to investigate the partitioning of airway contractility in the bronchioles of normoresponsive and hyperresponsive rats. Specifically, we addressed the questions 1) whether airway response to methacholine varied with airway size and 2) whether airways from rats known to be innately hyperresponsive to methacholine (Fisher) would have responses different from normoresponsive rats (Sprague-Dawley). We found that, in both strains of rats, contraction to methacholine occurred primarily in the medium- and larger-sized bronchioles (airways of diameter > 0.32 mm) and that, at the higher methacholine concentrations, the Fisher rats had greater degrees of contraction than did the Sprague-Dawley rats. These results suggest that the increased airway responsiveness seen in Fisher rats is due to an intrinsic increase in responsiveness (increased contractility) of their airways, which may be related to amount of smooth muscle, rather than an increase in airway sensitivity to methacholine. They do not, however, completely rule out the possibility of in vivo species-dependent differences in airway-parenchymal interactions.

scholarly journals Identification of Potential Radiation Responsive Metabolic Biomarkers in Plasma of Rats Exposed to Different Doses of Cobalt-60 Gamma Rays

Dose-Response ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 155932582097957
Author(s):  
Hua Zhao ◽  
Cong Xi ◽  
Mei Tian ◽  
Xue Lu ◽  
Tian-Jing Cai ◽  
...  
Keyword(s):  
Gamma Rays ◽  
Dose Response ◽  
Area Under The Curve ◽  
Rat Plasma ◽  
Dose Assessment ◽  
Sprague Dawley ◽  
Targeted Metabolomics ◽  
Response Curves ◽  
Sprague Dawley Rats ◽  
Metabolic Biomarkers

Metabolomics has great potential to process accessible biofluids through high-throughput and quantitative analysis for radiation biomarker screening. This study focused on the potential radiation responsive metabolites in rat plasma and the dose-response relationships. In the discovery stage, 20 male Sprague–Dawley rats were exposed to 0, 1, 3 and 5 Gy of cobalt-60 gamma rays at a dose rate of 1 Gy/min. Plasma samples were collected at 72 h after exposure and analyzed using liquid chromatography mass spectrometry based on non-targeted metabolomics. In the verification stage, 50 additional rats were exposed to 0, 1, 2, 3, 5 and 8 Gy of gamma rays. The concentrations of candidate metabolites were then analyzed using targeted metabolomics methods. Fifteen candidate radiation responsive metabolites were identified as potential radiation metabolite biomarkers. Metabolic pathways, such as linoleic acid metabolism and glycerophospholipid metabolism pathways, were changed after irradiation. Six radiation responsive metabolites, including LysoPC(20:2), LysoPC(20:3), PC(18:0/22:5), L-palmitoylcarnitine, N-acetylornithine and butyrylcarnitine, had good dose-response relationships ( R 2 > 0.80). The area under the curve of the panel of the 6 radiation responsive metabolites was 0.923. The radiation exposure metabolomics biomarkers and dose-response curves may have potential for rapid dose assessment and triage in nuclear and radiation accidents.

scholarly journals Notch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shusaku Maeda ◽  
Shigeru Miyagawa ◽  
Takuji Kawamura ◽  
Takashi Shibuya ◽  
Kenichi Watanabe ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Tissue Perfusion ◽  
Human Mesenchymal Stem Cell ◽  
Capillary Density ◽  
Adductor Muscle ◽  
Notch Signaling Pathway ◽  
Hindlimb Ischemia ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Whole Transcriptome Analysis

AbstractNotch signaling-modified human mesenchymal stem cell, SB623 cell, is a promising cell therapy product for ischemic stroke. With the aim to expand indications for their use for critical limb-threatening ischemia (CLTI), we hypothesized that SB623 cells improved tissue perfusion by inducing angiogenesis or arteriogenesis in a hindlimb ischemia model rat. In Sprague–Dawley rats, hindlimb ischemia was generated by femoral artery removal, then seven days after ischemic induction 1 × 105 SB623 cells or PBS was injected into the ischemic adductor muscle. As compared with the PBS group, tissue perfusion was significantly increased in the SB623 group. While capillary density did not vary between the groups, αSMA- and vWF-positive arterioles with a diameter  > 15 μm were significantly increased in the SB623 group. Whole transcriptome analysis of endothelial cells co-cultured with SB623 cells showed upregulation of the Notch signaling pathway as well as several other pathways potentially leading to arteriogenesis. Furthermore, rat muscle treated with SB623 cells showed a trend for higher ephrin-B2 and significantly higher EphB4 expression, which are known as arteriogenic markers. In the hindlimb ischemia model, SB623 cells improved tissue perfusion by inducing arteriogenesis, suggesting a promising cell source for treatment of CLTI.

Smooth muscle mechanical responses in vitro to bethanechol after progesterone in male rat.

1978 ◽  
Vol 235 (4) ◽  
pp. E422 ◽  
Author(s):  
L A Bruce ◽  
F M Behsudi ◽  
I E Danhof
Keyword(s):  
Smooth Muscle ◽  
Contractile Activity ◽  
Circular Muscle ◽  
Male Rat ◽  
Equal Weight ◽  
Muscarinic Agonist ◽  
Sprague Dawley ◽  
Response Curves ◽  
Dose Levels

Male Sprague-Dawley rats were pretreated subcutaneously with either progesterone (3 mg/kg per day) in a vehicle or a vehicle only for 3 days. Antral and gastroduodenal junctional tissues (GJT) were excised from both groups of animals and prepared for in vitro mechanical measurements. Responses from the circular muscle axis of these tissues were recorded with strain gauge transducers over a 30-min period. Chemical stimulation of the tissue was achieved with a muscarinic agonist, bethanechol chloride. Log-dose response curves suggested that untreated antral tissue generated stronger contractile activity than untreated GJT on an equal weight basis at bethanechol dose levels of 6.4 X 10(-6) M to 1 X 10(-4) M (P less than 0.005). Antral tissue and GJT contractile activity from the progesterone pretreated animals was significantly reduced (P less than 0.01) compared to the corresponding tissues from untreated animals at bethanechol dose levels of 6.4 X 10(-6) M and 1.28 X 10(-5) M. Progesterone pretreatment appeared to have little effect on the contractile frequency of either tissue. These results suggest possible progesteronic influences on contractile force in gastrointestinal smooth muscle.

Rosiglitazone reduces serum homocysteine levels, smooth muscle proliferation, and intimal hyperplasia in Sprague-Dawley rats fed a high methionine diet

Metabolism ◽  
2005 ◽  
Vol 54 (5) ◽  
pp. 645-652 ◽  
Author(s):  
Subramanyam N. Murthy ◽  
Demian F. Obregon ◽  
Natasha N. Chattergoon ◽  
Neil A. Fonseca ◽  
Debasis Mondal ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Intimal Hyperplasia ◽  
Sprague Dawley ◽  
Serum Homocysteine ◽  
Sprague Dawley Rats ◽  
Smooth Muscle Proliferation

scholarly journals Effects of adolescent caffeine consumption on cocaine self-administration and reinstatement of cocaine seeking

2018 ◽  
Vol 33 (1) ◽  
pp. 132-144
Author(s):  
Tracey A Larson ◽  
Casey E O’Neill ◽  
Michaela P Palumbo ◽  
Ryan K Bachtell
Keyword(s):  
Dose Response ◽  
Extinction Training ◽  
Schedules Of Reinforcement ◽  
Sprague Dawley ◽  
Self Administration ◽  
Caffeine Consumption ◽  
Adult Rats ◽  
Sprague Dawley Rats ◽  
Cocaine Seeking ◽  
Administration Procedure

Background: Caffeine consumption by children and adolescents has risen dramatically in recent years, yet the lasting effects of caffeine consumption during adolescence remain poorly understood. Aim: These experiments explore the effects of adolescent caffeine consumption on cocaine self-administration and seeking using a rodent model. Methods: Sprague-Dawley rats consumed caffeine for 28 days during the adolescent period. Following the caffeine consumption period, the caffeine solution was replaced with water for the remainder of the experiment. Age-matched control rats received water for the duration of the study. Behavioral testing in a cocaine self-administration procedure occurred during adulthood (postnatal days 62–82) to evaluate how adolescent caffeine exposure influenced the reinforcing properties of cocaine. Cocaine seeking was also tested during extinction training and reinstatement tests following cocaine self-administration. Results: Adolescent caffeine consumption increased the acquisition of cocaine self-administration and increased performance on different schedules of reinforcement. Consumption of caffeine in adult rats did not produce similar enhancements in cocaine self-administration. Adolescent caffeine consumption also produced an upward shift in the U-shaped dose response curve on cocaine self-administration maintained on a within-session dose-response procedure. Adolescent caffeine consumption had no effect on cocaine seeking during extinction training or reinstatement of cocaine seeking by cues or cocaine. Conclusions: These findings suggest that caffeine consumption during adolescence may enhance the reinforcing properties of cocaine, leading to enhanced acquisition that may contribute to increased addiction vulnerability.

Glutathione enhances endothelium-mediated control of coronary vascular resistance via a ROS- and NO intermediate-dependent mechanism

2012 ◽  
Vol 113 (2) ◽  
pp. 246-254 ◽  
Author(s):  
Andrew S. Levy ◽  
Chris Vigna ◽  
James W. E. Rush
Keyword(s):  
Vascular Resistance ◽  
Dose Response ◽  
Vascular Function ◽  
Soluble Guanylate Cyclase ◽  
Threshold Concentration ◽  
Coronary Vascular Resistance ◽  
Sprague Dawley ◽  
Response Curves ◽  
Physiological Relevance ◽  
Dependent Mechanism

The purpose of this investigation was to determine the effects of acute physiological GSH administration on endothelium-mediated reduction in coronary vascular resistance (CVR) using isolated perfused Sprague-Dawley rat hearts. A dose-response curve to GSH was conducted to determine a threshold concentration of GSH. We demonstrate that 30 μM GSH was sufficient to reduce CVR, and maximal dilation was achieved with 1 mM. In subsequent experiments, GSH was administered at concentrations of 0 [control (CON)], 1 μM, or 10 μM (GSH10), and dose-response curves to the endothelial agonist bradykinin (BK) were constructed. These GSH concentrations were chosen because of the physiological relevance and because the effects of GSH on BK action could be assessed independent of baseline differences in CVR. Sensitivity to BK (EC50) was enhanced in GSH10 vs. CON ( P < 0.05). This enhancement remained in the presence of nitric oxide (NO) synthase inhibition l-ωnitro-l-arginine (lNAME) and/or soluble guanylate cyclase (sGC) inhibition. Treatment with 4-hydroxy (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPOL) enhanced the sensitivity to BK in CON, similar to the effects of GSH10 and GSH10 + TEMPOL. However, the GSH10-dependent enhancement of EC50 observed in the presence of lNAME did not occur in the presence of lNAME + TEMPOL or in the presence of lNAME + sGC inhibition and NO scavenging. Collectively, these results suggest that GSH enhances BK-mediated dilation and reduction in CVR through an antioxidant-dependent mechanism that involves a NO intermediate but is unrelated to acute production of NO and GC-dependent effects of NO. These results suggest a mechanism whereby physiologically relevant levels of GSH modulate the endogenous reactive oxygen species and NO control of endothelium-dependent coronary vascular function.

Abstract 637: Hydrogen Sulfide Acts on Endothelial Cells to Elicit Dilation.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Nancy L Kanagy ◽  
Jessica M Osmond ◽  
Olan Jackson-Weaver ◽  
Benjimen R Walker
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Hydrogen Sulfide ◽  
Mesenteric Arteries ◽  
Direct Effects ◽  
Sprague Dawley ◽  
Imaging Studies ◽  
Knock Out ◽  
Event Frequency ◽  
Sprague Dawley Rats

Hydrogen sulfide (H 2 S), produced by the enzyme cystathionine-γ lyase (CSE), dilates arteries by hyperpolarizing and relaxing vascular smooth muscle cells (VSMC) and CSE knock-out causes hypertension and endothelial dysfunction showing the importance of this system. However, it is not clear if H 2 S-induced VSMC depolarization and relaxation is mediated by direct effects on VSMC or indirectly through actions on endothelial cells (EC). We reported previously that disrupting EC prevents H 2 S-induced vasodilation suggesting H 2 S might act directly on EC. Because inhibiting large-conductance Ca 2+ -activated K + (BK Ca ) channels also inhibits H 2 S-induced dilation, we hypothesized that H 2 S activates EC BK Ca channels to hyperpolarize EC and increase EC Ca 2+ which stimulates release of a secondary hyperpolarizing factor. Small mesenteric arteries from male Sprague-Dawley rats were used for all experiments. We found that EC disruption prevented H 2 S-induced VSMC membrane potential ( E m ) hyperpolarization. Blocking EC BK Ca channels with luminal application of the BK Ca inhibitor, iberiotoxin (IbTx, 100 nM), also prevented NaHS-induced dilation and VSMC hyperpolarization but did not affect resting VSMC E m showing EC specific actions. Sharp electrode recordings in arteries cut open to expose EC demonstrated H 2 S-induced hyperpolarization of EC while Ca 2+ imaging studies in fluor-4 loaded EC showed that H 2 S increases EC Ca 2+ event frequency. Thus H 2 S can act directly on EC. Inhibiting the EC enzyme cytochrome P 450 2C (Cyp2C) with sulfaphenazole also prevented VSMC depolarization and vasodilation. Finally, inhibiting TRPV4 channels to block the target of the Cyp2C product 11,12-EET inhibited NaHS-induced dilation. Combined with our previous report that CSE inhibition decreases BK Ca currents in EC, these results suggest that H 2 S stimulates EC BK Ca channels and activates Cyp2C upstream of VSMC hyperpolarization and vasodilation.

Histamine tachyphylaxis in canine airways despite prostaglandin synthesis inhibition

1988 ◽  
Vol 65 (5) ◽  
pp. 1944-1949 ◽  
Author(s):  
P. J. Antol ◽  
S. J. Gunst ◽  
R. E. Hyatt
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Prostaglandin Synthesis ◽  
Response Curves ◽  
Synthesis Inhibition ◽  
High Concentrations ◽  
Alpha Chloralose ◽  
Prostaglandin Synthesis Inhibitors

Tachyphylaxis to aerosolized histamine was studied in dogs anesthetized with thiamylal after pretreatment with prostaglandin synthesis inhibitors. Three consecutive histamine dose-response curves were obtained in nine dogs pretreated with 5 mg/kg indomethacin; two of these nine were also pretreated with 10 mg/kg indomethacin. Seven of the nine dogs were pretreated with 4 mg/kg sodium meclofenamate; four of these seven were also pretreated with 12 mg/kg. All dogs had tachyphylaxis at high concentrations of histamine regardless of inhibitor used. Pretreatment with indomethacin while the dogs were under alpha-chloralose-urethan anesthesia gave similar results. Histamine tachyphylaxis was also studied both in the presence and in the absence of indomethacin in tracheal smooth muscle strips obtained from seven additional dogs. A decrease in the median effective dose to histamine was observed in the indomethacin-treated strips, but tachyphylaxis to histamine remained. We conclude that prostaglandin synthesis inhibition does not reverse histamine tachyphylaxis either in vivo or in vitro. Thus the mechanism of histamine tachyphylaxis remains unexplained.

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