Abstract:
:Chronically hypoxic rats (exposed to 5000 m elevation for 3 weeks) develop pulmonary hypertension (PH) that is reversed upon return to normoxia and is blocked by bradykinin (BK) antagonist B9430 treatment (100 microg/kg s.c. three times per week). Treatment of rats with both the synthetic VEGF receptor-1/2 antagonist 3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-indolin-2-one (SU5416) (200 mg/kg, single s.c. injection) and hypoxia (3 weeks) causes irreversible severe PH characterized by marked elevation of pulmonary artery pressure (PAP), right ventricular hypertrophy, and obliteration of pulmonary arteries by proliferating endothelial cells (EC). Between weeks I and 2 of treatment, there is increased apoptotic EC death and caspase-3 activity. The combination of hypoxia with VEGFR-1 and -2 blockade appears to cause death of normal lung EC and proliferation of an apoptosis-resistant proliferating EC phenotype. Cotreatment with BK antagonist B9430 and (or) the broad caspase inhibitor Z-Asp-2,6-dichlorobenzoyloxymethylketone (Z-Asp) (2 mg/kg three times per week) prevented development of severe PH and caused significant reduction of PAP: 39.7 +/- 4.6 mmHg in Z-Asp + SU5416, 37.1 +/- 1.2 mmHg in BK antagonist B9430 + SU5416, 27.2 +/- 0.7 mmHg in Z-Asp alone, and 36.6 +/- 3.0 mmHg in BK antagonist alone versus 48 +/- 1.7 mmHg in SU5416-treated rats and 32.8 +/-1.4 mmHg in vehicle-treated controls. The PAP correlated with the right ventricular mass. Pulmonary arteries of rats treated with Z-Asp and BK antagonist B9430 had a marked reduction of intravascular EC, yet there was still evidence of medial muscular hypertrophy, similar to that observed in chronically hypoxic rats not treated with SU5416. We conclude that EC death induced by VEGFR-2 blockade with SU5416 may trigger an EC selection process that allows for the expansion of apoptosis-resistant EC, possibly driven by mechanisms independent of VEGF and VEGFR-2.
journal_name
Can J Physiol Pharmacoljournal_title
Canadian journal of physiology and pharmacologyauthors
Taraseviciene-Stewart L,Gera L,Hirth P,Voelkel NF,Tuder RM,Stewart JMdoi
10.1139/y02-047subject
Has Abstractpub_date
2002-04-01 00:00:00pages
269-74issue
4eissn
0008-4212issn
1205-7541journal_volume
80pub_type
杂志文章abstract::Pathogenic mechanisms for essential hypertension are unclear despite striking efforts from numerous research teams over several decades. Increased production of reactive oxygen species (ROS) has been associated with the development of hypertension and the role of ROS in hypertension has been well documented in recent ...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章,评审
doi:10.1139/y06-077
更新日期:2006-12-01 00:00:00
abstract::The experiment examined biological responses produced by combined sequential exposure to low-level tritium contamination, followed by challenging irradiation with fast neutrons. Modifications of endogenous antioxidant potential of different organs in rats were discussed in relation to tissue radiosensitivity. Rats pre...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y02-089
更新日期:2002-07-01 00:00:00
abstract::The objective of this study was to investigate under controlled conditions the effects of fentanyl on the rat locus coeruleus catechol oxidation current. Using differential normal pulse voltammetry combined with electrochemically treated carbon fiber electrodes to measure the catechol oxidation current, catecholamine ...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y89-085
更新日期:1989-05-01 00:00:00
abstract::Pertussis toxin (PTX) is a heterohexameric protein, which is divided into subunits A and B. The A-subunit (protomer) possesses adenine diphosphate (ADP) ribosyltransferase activity, and the B-oligomer confers cell surface binding specificity on the toxin. By virtue of the ADP-ribosylation activity in the A-subunit, PT...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/cjpp-74-5-559
更新日期:1996-05-01 00:00:00
abstract::In sepsis, systemic inflammatory response syndrome (SIRS), and multiorgan dysfunction syndrome (MODS), a severe prognostically relevant cardiac autonomic dysfunction exists, as manifested by a strong attenuation of sympathetically and vagally mediated heart rate variability (HRV). The mechanisms underlying this attenu...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章,评审
doi:10.1139/Y09-012
更新日期:2009-04-01 00:00:00
abstract::Hereditary muscular hypertrophy is a character that has been selected in several animal species for industrial meat production. The selection of this character in cattle produces animals of exceptional commercial value but ones with a lower aerobic capacity than that of conventional cattle. The purpose of this work wa...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y93-143
更新日期:1993-12-01 00:00:00
abstract::Changes in metabolic characteristics of the liver and jejunal epithelia as a result of feeding the beta-agonist albuterol to chickens for 3 and 6 weeks were studied. Feeding albuterol resulted in a change in weights of the liver and small intestines. Chickens fed albuterol for 6 weeks had greater levels of plasma none...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y89-069
更新日期:1989-05-01 00:00:00
abstract::In experiments on isolated guinea pig papillary muscles the effects of verapamil (5 mg/L) and caffeine (1 g/L) on the two-component contraction were investigated. The muscles were continuously superfused with normal Tyrode's solution containing 2 mg of noradrenaline/L at 20--22 degrees C. The first derivative of contr...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y79-132
更新日期:1979-08-01 00:00:00
abstract::The combined and separate effects of exercise training and bisphosphonate (etidronate) therapy on bone mineral in postmenopausal women were compared. Forty-eight postmenopausal women were randomly assigned (double blind) to groups that took intermittent cyclical etidronate; performed strength training (3 d/week) and r...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1139/y02-126
更新日期:2002-10-01 00:00:00
abstract::Single crab (Callinectes danae) fibers were equilibrated with isotonic, high KCl solutions and were subsequently returned to the control saline. This caused marked swelling of the T tubules. Fibers treated with 100 mM KCl had a 2.5-mV residual depolarization, a 50% decrease in effective membrane resistance (Reff) and ...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y85-144
更新日期:1985-07-01 00:00:00
abstract::The effect of chronic consumption of diets containing either different sources of dietary fibre (8% guar, 8% pectin, or 8% multifibre) or low carbohydrate upon carbohydrate tolerance was examined in rats. Weight gain was significantly lower throughout the entire 28-day study period with the guar group and after 20 day...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y82-107
更新日期:1982-06-01 00:00:00
abstract::The hypotensive effect of clonidine in anaesthetised (pentobarbitone) cat has been analysed with the help of pharmacological tools. Application of clonidine (0.1%) to the exposed ventral surface of medulla oblongata produced hypotension (28.6%) and bradycardia (18%). Similar application of glycine (5%) and GABA (10%) ...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y77-138
更新日期:1977-10-01 00:00:00
abstract::Poly(N alpha, N epsilon-L-lysinediylterephthaloyl) (PPL) microcapsules containing sheep erythrocyte hemolysate (mean diameter, 380 nm) were prepared by an interfacial polymerization technique using electrocapillary emulsification as the means of producing very fine hemolysate droplets to be encapsulated. Measurements ...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y80-030
更新日期:1980-02-01 00:00:00
abstract::Microelectrode and mechanical studies were performed with isolated guinea pig myocardium (right ventricular free walls and papillary muscles) to examine the effects of platelet-activating factor (PAF) and lysophosphatidylcholine (LPC). Low concentrations of PAF (10(-8) to 10(-6) M, a range equivalent to the blood conc...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y89-107
更新日期:1989-06-01 00:00:00
abstract::Our objective was to determine the effects of a clenbuterol (CB) treatment orally administered (2 mg per kg) to rats submitted to 14 days of hindlimb unloading (HU). The morphological and the contractile properties as well as the myosin heavy chain isoforms contained in each fiber type were determined in whole soleus ...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y04-034
更新日期:2004-05-01 00:00:00
abstract::A possible implication of endogenously released ATP and (or) ADP in insulin response to glucose stimulation was investigated in the isolated rat pancreas. The first phase of insulin response to the same glucose concentration (8.3 mM) was much higher in pancreas previously perfused in the absence of glucose than in pan...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y93-086
更新日期:1993-08-01 00:00:00
abstract::Activity-related transient changes in extracellular K+ concentration ([K+]c), extracellular pH (pHc), and extracellular volume (EC volume) were studied by means of ion-selective microelectrodes in the adult rat spinal cord in vivo and in neonatal rat spinal cords isolated from pups 3-14 days of age. Repetitive electri...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章,评审
doi:10.1139/y92-276
更新日期:1992-01-01 00:00:00
abstract::We compared the determinants of spontaneous activity in explanted neonatal (2-day-old) rat ventricle cells and in reaggregates derived from 15-day-old chick embryos. We studied the beating rate with an optical recording method and the underlying electrical activity with glass microelectrodes using the K current blocke...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y89-126
更新日期:1989-07-01 00:00:00
abstract::Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain. In this study, we investigated the antiseptic effects and underlying mechanisms of vicenin-2 and scolymoside, which are 2 active compounds from C. subternata that act against high mobility group box 1 (HMGB1)-mediated septi...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/cjpp-2015-0021
更新日期:2015-08-01 00:00:00
abstract::In 2-kidney, 1-clip hypertensive rats, the time course of changes in blood pressure (BP), heart rate, activity of the sympathetic nervous system and the renin-angiotensin system, plasma and blood volumes, left ventricular (LV) and right ventricular (RV) weight, and LV dimensions were evaluated during treatment with hy...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y86-257
更新日期:1986-12-01 00:00:00
abstract::Hepatotoxicity and nephrotoxicity are important drawbacks of cisplatin. The objective of this study is to evaluate the ability of ambroxol in 2 different doses (35 and 70 mg/kg, i.p.) to protect liver and kidney from damage induced by a single dose of cisplatin (10 mg/kg, i.p.) in comparison with N-acetylcysteine (250...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/cjpp-2018-0528
更新日期:2019-01-01 00:00:00
abstract::Grains are global dietary staples that when consumed in whole grain form, offer considerable health benefits compared with milled grain foods, including reduced body weight gain and reduced cardiovascular and diabetes risks. Dietary patterns, functional foods, and other lifestyle factors play a fundamental role in the...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章,评审
doi:10.1139/cjpp-2012-0351
更新日期:2013-06-01 00:00:00
abstract::Intra- and extra-cellular concentrations of calcium were measured in hippocampal neurons of areas CA1 and CA3 during 8 min ischaemia and short-term (up to 60 min) recovery. During an ischaemic insult, [Ca2+]i increased progressively and [Ca2+]e decreased. There were large interneuronal differences, although, in genera...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y92-262
更新日期:1992-01-01 00:00:00
abstract::In both isolated canine ventricular trabecular muscle and Purkinje strand preparations, dl-sotalol and its two optical isomers d- and l-sotalol produced a concentration-dependent increase in action potential duration while other transmembrane electrical characteristics were not significantly affected. The magnitude of...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y85-248
更新日期:1985-12-01 00:00:00
abstract::Studies were conducted to determine whether Na-K ATPase or a second species of digitalis receptors in canine cardiac sarcolemma membrane preparations is associated with the positive inotropic action of nontoxic concentrations of ouabain. [3H]ouabain association and dissociation experiments using highly enriched sarcol...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y85-083
更新日期:1985-05-01 00:00:00
abstract::The present study focused on the interactive pain regulation of endokinin A/B (EKA/B, the common C-terminal decapeptide in EKA and EKB) or endokinin C/D (EKC/D, the common C-terminal duodecapeptide in EKC and EKD) on chimeric peptide MCRT (YPFPFRTic-NH2, based on YPFP-NH2 and PFRTic-NH2) at the supraspinal level in mi...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/cjpp-2015-0554
更新日期:2016-09-01 00:00:00
abstract::The potential of nickel chloride to prevent streptozotocin-induced hyperglycemia was tested in rats in vivo. To induce diabetes, streptozotocin (100 mg/kg body weight) was injected as a single dose. Streptozotocin treatment resulted in a significant decrease in plasma insulin and ceruloplasmin, and pancreatic Cu, prot...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y88-104
更新日期:1988-05-01 00:00:00
abstract::The effect of one bout of acute exercise on impaired glucose metabolism was studied in obese (480 +/- 20 g), untrained rats, at rest (n = 10) and after 60 min of swimming (n = 5). Using the euglycemic, hyperinsulinemic (10 mU.kg-1 x min-1) clamp, glucose clearance rate increased from 7.6 +/- 0.9 at rest to 9.7 +/- 0.5...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y92-208
更新日期:1992-11-01 00:00:00
abstract::A brief burst of electrical stimuli delivered to the vagus nerve during the cardiac cycle elicits a triphasic cardiac chronotropic response. The cardiac cycle length initially increases, then briefly decreases, and subsequently increases again. We studied the effects of a calcium channel blocking agent, verapamil, on ...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y86-164
更新日期:1986-07-01 00:00:00
abstract::Despite major advances in conventional medical therapy, patients with heart failure continue to experience significant morbidity and mortality. Endothelin-1 (ET-1) is a potent vasocontrictor and mitogenic peptide that is activated in heart failure. There is increasing experimental and clinical evidence in support of a...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章,评审
doi:10.1139/y03-011
更新日期:2003-06-01 00:00:00