Abstract：
:The objective of the present study was to assess the cardioprotective effect of dual NEP-ACE inhibition in relation to endogenous cardiac bradykinin (BK), its active metabolite des-Arg9-BK, endogenous brain natriuretic peptides (BNP), and cGMP. Rats were treated with the dual metallopeptidase inhibitor, omapatrilat, or the ACE inhibitor, ramipril, for 7 d (1 mg.kg(-1).d(-1)). Hearts were then isolated and subjected to a zero-flow ischemia and reperfusion (except controls), in the absence or presence of either a B2-receptor antagonist (Hoe-140), a B1-receptor antagonist (Lys-Leu8-des-Arg9-BK), or the GC-A/GC-B-receptor antagonist (HS-142-1). Chronic omapatrilat and ramipril increased the amount of endogenous BK collected upon reperfusion, but only ramipril increased that of des-Arg9-BK. Only omapatrilat increased both peak BNP and peak cGMP upon reperfusion, those increases being blocked by Hoe-140. Chronic omapatrilat (but not ramipril) decreased the total noradrenaline and lactate dehydrogenase release during the reperfusion period. Importantly, only omapatrilat improved the functional recovery of the ischemic reperfused heart, with a reduced left ventricular end-diastolic pressure, and improved developed left ventricular pressure. All cardio protective effects of omapatrilat were blocked by Hoe-140 and by HS-142-1, but not by the B1-receptor antagonist. In conclusion, a chronic treatment with a dual metallopeptidase inhibitor demonstrated a cardioprotective action not observed with an ACE inhibitor in a context of severe ischemia in rat isolated hearts, which was mediated by both endogenous BK and BNP.
journal_name
Can J Physiol Pharmacoljournal_title
Canadian journal of physiology and pharmacologyauthors
Dumoulin MJ,Adam A,Burnett J,Heublein D,Yamaguchi N,Lamontagne Ddoi
10.1139/y04-134subject
Has Abstractpub_date
2005-02-01 00:00:00pages
166-73issue
2eissn
0008-4212issn
1205-7541pii
y04-134journal_volume
83pub_type
杂志文章abstract：:The lysosomal protease cathepsin D increased markedly in brown adipocytes during differentiation in primary cultures. Differentiated cells had 20 times the amount of immunoreactive cathepsin D found in preadipocytes. Cathepsin D mRNA, as estimated by relative RT-PCR, was also present in higher amounts in differentiate...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y02-067
更新日期：2002-06-01 00:00:00
abstract：:The present study was conducted to evaluate the local antinociceptive actions of fluoxetine, a selective serotonin reuptake inhibitor, and the possible involvement of the l-arginine/NO/cGMP/KATP channel pathway in this effect using the formalin test in rats. To elucidate the underlying mechanisms, animals were pre-tre...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2017-0003
更新日期：2018-02-01 00:00:00
abstract：:The vasoconstrictors norepinephrine (NE) and angiotensin II (AII) mediate increases in oxygen uptake (VO2) by the constant flow perfused rat hind limb that are inhibited by quinidine-like membrane-stabilizing effects (involving the interruption of action potential) of (+/-)-propranolol with little effect on vasoconstr...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：1998-02-01 00:00:00
abstract：:While conducting studies on the prevention of mortality from acute iron intoxication in rats, diazepam, given to prevent animal suffering, was observed to be associated with reduced mortality in a limited number of animals. The objective was to assess whether diazepam reduces mortality following acute iron intoxicatio...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-76-9-895
更新日期：1998-09-01 00:00:00
abstract：:New methods for chronic instrumentation of the newborn piglet are described, which allow continuous monitoring of not only pressures in the pulmonary artery and aorta but also in the left and right atria, pulmonary vein, as well as main branch pulmonary artery flows. Changes in pulmonary vascular tone to short-acting ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y87-126
更新日期：1987-05-01 00:00:00
abstract：:We examined the interaction of smooth muscle myosin with alpha-actin and beta-actin isoforms during the contraction of A7r5 smooth muscle cells and rat aortic smooth muscle. The techniques of confocal microscopy and fluorescence resonance energy transfer (FRET) analysis were utilized in examining A7r5 cells and rat ao...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y09-008
更新日期：2009-05-01 00:00:00
abstract：:A simple method using gas chromatography-mass spectrometry was developed to determine a low concentration of ethanol in urine. The detection limit was 0.02 mM ethanol. A mean +/- SD ethanol concentration in urine of 0.21 +/- 0.17 mM was measured in 11 alcoholics after 14 days abstention, a level at least 10 times high...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y87-193
更新日期：1987-06-01 00:00:00
abstract：:Effect of Ni2+ on Zn2+-induced potentiation of twitch tension was studied electrophysiologically in the toe muscle fibers of Rana catesbeiana. The major findings of this investigation are as follows. When 2 mM Ni2+ was applied to fibers in a normal Ringer's solution containing 50 microM Zn2+ (Zn2+ solution), the Zn2+-...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y86-104
更新日期：1986-05-01 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：:The purpose of this study was to determine the interaction of three factors that modify twitch contraction amplitude in the rat gastrocnemius muscle in situ: posttetanic potentiation, fatigue, and caffeine. Posttetanic (200 Hz for 1 s) twitch responses were observed before and after 15 Hz stimulation for 6 min (group ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y87-046
更新日期：1987-02-01 00:00:00
abstract：:Taurine status and pregnancy outcome were assessed in rats fed low dietary taurine and varying doses of guanidinoethyl sulfonate (GES), a structural analogue of taurine. Female Sprague-Dawley rats (225-270 g) were mated overnight and assigned to one of four groups from day 0 to 20 of gestation. Taurine-deficient anima...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y95-161
更新日期：1995-08-01 00:00:00
abstract：:Resting membrane potentials and membrane conductances of chick skeletal muscle in culture were determined from the 3rd to the 10th day after plating. The effect of tetraethylammonium (TEA) and of replacement of potassium with caesium on these parameters was investigated. Resting membrane potential (Em) rises during my...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y80-100
更新日期：1980-06-01 00:00:00
abstract：:The effects of oxytocin (OT) on holding current were studied in uterine smooth muscle cells freshly isolated from the longitudinal layer of 18-20 day pregnant rats, using the nystatin method of whole-cell voltage clamp. As we previously reported, the voltage-dependent Ca2+ current (L type) was partially inhibited by O...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y94-108
更新日期：1994-07-01 00:00:00
abstract：:Most physiological and pathophysiological responses to bradykinin are mediated by G-protein-coupled receptors designated B2 receptors. Discovery of antagonists for these receptors has brought about a revolution in research in the kinin field. The chemistry and development of antagonists for B2 kinin receptors are disc...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/y95-106
更新日期：1995-07-01 00:00:00
abstract：:The alcohol oxidase membrane technique is available for measurement of ethanol in commercial fluids. In this paper we examined its usefulness for cat and human blood in comparison with gas-liquid chromatography (GLC). The membrane method proved to be simple, reproducible, accurate, and inexpensive. Analysis took 1-2 m...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y88-052
更新日期：1988-04-01 00:00:00
abstract：:Altered sympathetic nervous activity has been linked to the development and persistence of obesity, partly relating to overfeeding. Binding of the selective, positron-emitting phosphodiesterase-4 (PDE4) inhibitor (R)-[11C]rolipram provides a direct index of the cAMP-hydrolyzing enzyme PDE4. This study examines progres...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y09-001
更新日期：2009-03-01 00:00:00
abstract：:The area postrema (AP) is one of the circumventricular organs of the brain and as such it is highly vascular and lacks the normal blood-brain barrier. Anatomical tracing studies have demonstrated afferent projections to AP originating from the paraventricular nucleus, lateral parabrachial nucleus (l-PBN), nucleus trac...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/y91-153
更新日期：1991-07-01 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：:Using immunofluorescence and real 3-D confocal microscopy, our results showed the presence of ET-1, ETA, and ETB receptors in isolated human aortic vascular endothelial cells (hVECs). The level of the peptide and its receptors was significantly higher in the nucleus (including the nuclear envelope membranes) than in t...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/Y10-057
更新日期：2010-08-01 00:00:00
abstract：:We tested the effects of inhibiting the carbonic anhydrase activity of rat soleus and extensor digitorum longus muscles on the isometric contractile properties and the resistance to fatigue. SOL and EDL muscles from female rats were incubated in vitro in the presence of methazolamide, a specific inhibitor of carbonic ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y89-103
更新日期：1989-06-01 00:00:00
abstract：:This study investigated the effects of prolonged exercise on muscle sarcoplasmic reticulum (SR) Ca2+ cycling properties and the metabolic responses with and without a session of exercise designed to reduce muscle glycogen reserves while on a normal carbohydrate (CHO) diet. Eight untrained males (VO(2peak) = 3.81 +/- 0...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 临床试验,杂志文章
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更新日期：2005-07-01 00:00:00
abstract：:The effect of high potassium depolarization on the release of exogenously supplied [3H]glutamate and endogenous glutamate from tissue slices of the cestode Hymenolepis diminuta was examined. Increasing concentrations of potassium stimulated the release of radiolabel from tissues preloaded with [3H]glutamate. This rele...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y88-145
更新日期：1988-07-01 00:00:00
abstract：:Our objective was to investigate the effects of chronic excess iodine intake on thyroid functions and thyroid oxidative stress state in hypothyroid rats. Sixty rats were divided into euthyroid and hypothyroid (thiocyanate-induced) groups with or without administration of excess iodine (3000 or 6000 μg/L) for 8 weeks. ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y2012-046
更新日期：2012-05-01 00:00:00
abstract：:Blood pressure fluctuates continuously throughout life and autoregulation is the primary mechanism that isolates the kidney from this fluctuation. Compared with Wistar rats, Brown Norway (B-N) rats display impaired renal myogenic autoregulation when blood pressure fluctuation is increased. They also are very susceptib...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：2001-03-01 00:00:00
abstract：:Altered cytochrome P450-catalyzed metabolism of 17beta-estradiol (E2) and estrone (E1) in the liver and (or) extrahepatic tissues may affect estrogen-sensitive tumorigenesis. We examined the effects of oral treatments of (i) indole-3-carbinol (13C) at 250 or 500 mg/kg or beta-naphthoflavone (beta-NF) at 40 mg/kg of bo...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：2001-06-01 00:00:00
abstract：:Ischemic heart disease is the leading cause of morbi-mortality in developed countries. Both ischemia-reperfusion injury and mechanisms of cardioprotection have been studied for more than 50 years. It is known that the physiopathological mechanism of myocardial ischemia involves several factors that are closely related...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/y2012-085
更新日期：2012-09-01 00:00:00
abstract：:The metabolic effect of intravenous infusion of ammonium chloride (60 mumol/(kg body weight.min] was compared in five sheep before and after adrenal denervation. Adrenal denervation completely abolished the hyperglycemic effect of ammonium chloride, diminished the rise of pyruvate and lactate concentration, and failed...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y89-168
更新日期：1989-09-01 00:00:00
abstract：:The aim of the present study was to investigate the protective effect of total flavones of rhododendra (TFR) pharmacological preconditioning against myocardial ischemia-reperfusion (I/R) injury and its probable mechanisms in rats. Rat myocardial I/R injury was induced by ligating and untying the left anterior descendi...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y08-016
更新日期：2008-03-01 00:00:00
abstract：:Cardiac adenosine receptors are coupled to adenylate cyclase inhibition. In the guinea pig heart, the relative agonist potencies observed for adenylate cyclase inhibition were R-N6-phenylisopropyladenosine (R-PIA) = N6-cyclohexyladenosine greater than 5'-N-ethylcarboxamidoadenosine much greater than S-PIA. In both atr...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y86-252
更新日期：1986-12-01 00:00:00
abstract：:Androgens have been reported to stimulate progesterone production by granulosa cells of several species, and to act synergistically with FSH in stimulation of progesterone accumulation by rat granulosa cells. Studies were undertaken to examine the effect of androgens on FSH-stimulated progesterone production in cultur...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y84-138
更新日期：1984-07-01 00:00:00
