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Canadian Journal of Physiology and Pharmacology

Leila Safaeian, Golnaz Vaseghi, Hedieh Jabari, Nasim Dana
The proprotein convertases family is involved in several physiological processes such as cell growth, migration, and angiogenesis, and also in different pathological conditions. Evolocumab, an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9), has recently been approved for treatment of hypercholesterolemia. This study aimed to investigate the effect of evolocumab on angiogenesis in human umbilical vein endothelial cells (HUVECs). Cell proliferation and migration were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell methods...
March 15, 2019: Canadian Journal of Physiology and Pharmacology
Mirna N Chahine, Simon Toupance, Sandy El-Hakim, Carlos Labat, Sylvie Gautier, Toufic Moussallem, Pierre Yared, Roland Asmar, Athanase Benetos
Short telomere length (TL) is associated with atherosclerotic cardiovascular disease (ACVD) and other age-related diseases. It is unclear whether these associations originate from having inherently short TL or a faster TL attrition before or during disease development. We proposed the blood-and-muscle model to assess TL dynamics throughout life course. Our objective was to measure TL in leukocytes (LTL) and in skeletal muscle (MTL), which served as a proxy of TL at birth. The delta (MTL-LTL) represented life-long telomere attrition...
March 15, 2019: Canadian Journal of Physiology and Pharmacology
Ming Yang, Ke Zhang, Xuefang Zhang, Zhen Zhang, Xinhua Yin, Gaole He, Liang Li, Xiaobin Yang, Baorong He
The present study was undertaken to explore the therapeutic potential of hydrogen sulfide (H2S) against bone loss induced by modeled microgravity. Hind-limb suspension (HLS) and rotary wall vessel bioreactor (RWVB) were applied to model microgravity in vivo and in vitro, respectively. Treatment of rats with GYY4137 (a water soluble donor of H2S, 25mg/kg/day, i.p.) attenuated HLS-induced reduction of bone mineral density in tibiae, and preserved bone structure in tibiae and mechanical strength in femurs. In HLS group, GYY4137 treatment significantly increased levels of osteocalcin in sera...
March 14, 2019: Canadian Journal of Physiology and Pharmacology
Moni Nader, Ebtehal Alsolme, Shahad Alotaiby, Rahmah Alsomali, Dana Bakheet, Nduna Dzimiri
Structural dilation of cardiomyocytes (CMs) imposes a decline in cardiac performance that precipitates cardiac failure and sudden death. Since membrane proteins are implicated in dilated cardiomyopathy and heart failure, we evaluated the expression of the sarcolemmal membrane-associated protein (SLMAP) in dilated cardiomyopathy and its effect on CM contraction. We found that all three SLMAP isoforms (SLMAP-1, -2, and -3) are expressed in CMs and are downregulated in human dilated ventricles. Knockdown (KD) of SLMAPs in cultured CMs transduced with recombinant adeno-associated viral particles (AAV) releasing SLMAP-shRNA precipitated reduced spontaneous contractile rate that was not fully recovered in SLMAP-depleted CMs challenged with isoproterenol (ISO), thus phenotypically mimicking heart failure performance...
March 11, 2019: Canadian Journal of Physiology and Pharmacology
Nanees Fouad El-Malkey, Nourelhuda A Mohammed, Amal Al-Shahat Ibrahim, Doaa M Abdullah
The effect of vitamin D on cardiac dysfunction after menopause is still under investigation. Therefore, we investigated the effect of vitamin D3 on cardiac apoptotic and structural changes in ovariectomized rats. Forty adult female albino rats were divided into 4 equal groups: sham rats, sham rats treated with vitamin D3, ovariectomized rats and ovariectomized rats treated with vitamin D3 (500 IU/kg/day/6 weeks, orally). Body weight, blood pressure, heart rate and whole heart weight (WHW) were measured. Serum soluble receptors of advanced glycation end products (sRAGE), C-reactive protein (CRP), malondialdehyde and total antioxidant capacity (TAC) were estimated...
March 11, 2019: Canadian Journal of Physiology and Pharmacology
Kamal M Kassem, Sonal Vaid, Hongmei Peng, Sarah Sarkar, Nour-Eddine Rhaleb
The last 20 years witnessed the emergence of the thymosin 4 (T4)-N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) pathway as a new source of future therapeutic tools to treat cardiovascular and renal diseases. In this review article, we attempted to shed light on the numerous experimental findings pertaining to the many promising cardiovascular therapeutic avenues for the T4 and/or its N-terminal derivative, Ac-SDKP. Specifically, Ac-SDKP is endogenously produced from the 43-amino acid Tβ4 by two successive enzymes meprin α and prolyl oligopeptidase (POP)...
March 9, 2019: Canadian Journal of Physiology and Pharmacology
Noha Mohamed Badae, Asmaa Samy El Naggar, Samiha Mahmoud El Sayed
Myocardial infarction (MI) is a major cause of cardiac dysfunction. All components of the cardiac renin angiotensin system (RAS) are upregulated in MI. Angiotensin converting enzyme (ACE) and ACE2 are key enzymes involved in synthesis of components of RAS and provide a counter-regulatory mechanism within RAS. We compared the cardioprotective effect of the ACE2 activator diminazene aceturate (DIZE) versus the ACE inhibitor (enalapril) on post acute myocardial infarction (AMI) ventricular dysfunction in rats...
March 6, 2019: Canadian Journal of Physiology and Pharmacology
Mohammed Heikal, Ahmed Shaaban, Wagdi ELkashef, Tarek Ibrahim
Objective-To test the potential anti-oxidant and anti-inflammatory effects of febuxostat and/or stopping high-fat diet on the biochemical parameters of high fat diet-induced hyperlipidemic rabbits. Background-Febuxostat, a highly potent xanthine oxidase inhibitor with antioxidant effect, inhibits elevated xanthine oxidase, leading to reduction of reactive oxygen species (ROS) and oxidative stress, the main causes of vascular inflammation in hyperlipidemia. Methods- Male New Zealand rabbits were distributed in three groups: normal control (NC) fed standard chow for 12 weeks; the other two groups fed high-fat diet (HFD) with 1% cholesterol for 8 weeks, and then shifted to standard chow for 4 weeks...
March 1, 2019: Canadian Journal of Physiology and Pharmacology
Cennet Balcilar, Isil Ozakca-Gunduz, Vecdi Melih Altan
Diabetes-induced endothelium damage leads to vascular dysfunction. The current study was designed to determine the effects of short-term (4-week) streptozotocin (STZ)-induced diabetes on endothelium-derived contracting factors (EDCF)-mediated responses with possible contributions of Rho-kinase and AMP-activated kinase (AMPK) signaling pathways. The effects of STZ-diabetes on vascular functions were examined in isolated thoracic aorta preparations of 30-week-old rats. The diabetes-associated changes in vascular function were studied with calcium ionophore A23187, acetylcholine, Rho-kinase inhibitor Y27632 and AMPK activator AICAR...
February 20, 2019: Canadian Journal of Physiology and Pharmacology
Naoki Makino, Toyoki Maeda, Nobuyuki Abe
Telomere shortening is well known to be associated with the aging process and aging-associated diseases, including diabetes. The telomere length and subtelomeric methylation status in peripheral leucocytes (LTL) were compared in elderly type 2 diabetes patients (T2D) and diabetes free controls (C). The methylation status was analyzed the between of MspI-TRF lengths and HpaII-TRF lengths by using methylation-sensitive and -insensitive restriction enzyme isoschizomers, MspI and HpaII, respectively. Although the mean telomere lengths, MspI-TRF or HpaII-TRF, were no difference in patients between C and T2D...
February 20, 2019: Canadian Journal of Physiology and Pharmacology
Bojana Stefanovic, Natasa Spasojevic, Predrag Jovanovic, Sladjana Dronjak
This study investigated the effects of melatonin treatment on adrenal catecholamine content, synthesis, uptake and vesicular transport induced by the chronic unpredictable mild stress (CUMS) model of depression in rats. This entailed quantifying the norepinephrine, epinephrine, mRNA and protein levels of tyrosine hydroxylase (TH), dopamine-b-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2) in the adrenal medulla...
February 16, 2019: Canadian Journal of Physiology and Pharmacology
Biljana Jakovljevic, Tamara R Nikolic Turnic, Nevena Jeremic, Maja Savic, Jovana Jeremic, Ivan M Srejovic, Branislav Belic, Nenad Ponorac, Vladimir Jakovljevic, Vladimir I Zivkovic
This study was aimed to assess the impact of high intensity interval training (HIIT) vs. moderate intensity continious training (MIT) on cardiodynamic parameters in isolated rat heart. Wistar albino rats were randomly assigned to groups according to running protocol: sedentary control (CTRL), MIT, HIIT; spontaneous hypertensive sedentary control (SHR), spontaneous hypertensive rats (SHR) + MIT and SHR + HIIT. HIIT groups performed the running in 5 sprints x 45-55m/min for 30-90sec, with 2 mins rest after each sprint, while MIT groups performed the running of 10-15m/min for 1h with 3 mins rest/100m, both protocols were implemented 5 days/week over 4 weeks with one week of adaptation before protocols started...
February 8, 2019: Canadian Journal of Physiology and Pharmacology
Kouichi Yamamoto, Atsushi Yamatodani
We previously reported that sevoflurane-induced pica, kaolin ingestion behavior, in rats has the potential to reflect post-operative nausea and vomiting (PONV) in humans. It is well-known that corticosteroids, which inhibit both prostaglandin and leukotriene syntheses due to phospholipase A2 inhibition, are effective for reducing PONV; however, the precise mechanisms remain unclear. We investigated the involvement of the prostaglandin or leukotriene pathway in the development of sevoflurane-induced pica. We found that sevoflurane-induced pica was effectively inhibited by pretreatment with a leukotriene receptor antagonist (montelukast) or an inhibitor of 5-lipoxygenase (zileuton), rather than an inhibitor of cyclooxygenase (flurbiprofen)...
February 7, 2019: Canadian Journal of Physiology and Pharmacology
Danielle Jacques, Chantale Provost, Alexandre Normand, Nadia Abou Abdallah, Johny Al-Khoury, Ghassan Bkaily
Endocardial endothelial cells (EECs) form a monolayer lining the ventricular cavities. Studies from our laboratory and the literature have shown differences between EECs isolated from the right and left ventricles (EECRs and EECLs respectively). Angiotensin II (Ang II) was shown to induce apoptosis of different cell types mainly via AT1 receptor activation. In this study, we verified whether Ang II induces apoptosis of human EECRs and EECLs and via which type of receptor. Using the Annexin V labeling and in situ TUNEL assays, our results showed that Ang II-induced apoptosis of both hEECRs and hEECLs in a concentration-dependent manner...
February 7, 2019: Canadian Journal of Physiology and Pharmacology
Deniz Kaleli-Durman, Fatoş Ilkay Alp-Yıldırım, Osman Özdemir, B Sönmez Uydeş-Doğan
Statins are determined to have various pleiotropic effects apart from their lipid lowering properties. Herein, we investigated the direct effects of atorvastatin on gastric smooth muscle tone. Atorvastatin effectively relaxed isolated rat gastric fundus strips precontracted with acetylcholine, potassium chloride and serotonin. Incubation of the strips with nitric oxide (NO) synthase inhibitor, L-NOARG (10-4M,20 min.), L-type voltage- operated Ca2+ channel (VOCC) blocker, nifedipine (10-6M,30 min.), KATP channel blocker, glibenclamide (10-5M,30 min...
February 7, 2019: Canadian Journal of Physiology and Pharmacology
Milan Potić, Ivan Ignjatović, Vanja Nickovic, Jovan B Živković, Jelena Krdžić, Jadranka Mitić, Dejan Popović, Ivan Ilić, Nikola Stojanovic, Dusan Sokolovic
Acute kidney injury (AKI) is a frequent disorder that can be mimicked by the application of different nephrotoxic agents, including carbon tetrachloride (CCl4), where kidney injury marker-1 (KIM-1) has been recognized as a highly specific marker. Melatonin represents one of the most powerful natural antioxidants which has numerous beneficial properties. We evaluated the nephroprotective potential of two melatonin-treatment (pre- and post-intoxication) regimens in a CCl4-induced AKI model based on the standard serum parameters, kidney tissue antioxidative capacity, KIM-1 levels, and kidney tissue morphological changes...
February 7, 2019: Canadian Journal of Physiology and Pharmacology
Ebru Çetin
This study was conducted to investigate the possible protective effects of ghrelin against tilmicosin-induced acute ventricular dysfunction in rats. Forty adult male Sprague-Dawley rats were randomly divided into four equal groups: the control, ghrelin, tilmicosin and ghrelin plus tilmicosin groups. The left ventricular structural and functional parameters with together cardiac biomarker levels were evaluated. The results showed that tilmicosin treatment alone significantly decreased the left ventricular fractional shortening (LVFS), left ventricular ejection fraction (LVEF), left ventricular stroke volume (LVSV) and cardiac output (CO) when compared to control group...
February 6, 2019: Canadian Journal of Physiology and Pharmacology
Vera B Plakhova, Valentina A Penniyaynen, Igor L Yachnev, Ilya V Rogachevskii, Svetlana A Podzorova, Boris V Krylov
Low-power (non-thermal) infrared (IR) radiation with the wavelength of 10.6 µm activates the Na,K-ATPase transducer function in sensory neurons, which is manifested in decrease of NaV1.8 channel voltage sensitivity at the cellular membrane level and in inhibition of growth of chick embryo dorsal root ganglia neurites at the tissue level. It is shown that the effect of low-power IR radiation is totally blocked by a specific Src kinase inhibitor PP2. Upon irradiation on the background of PP2, the effective charge of NaV1...
February 2, 2019: Canadian Journal of Physiology and Pharmacology
Natalia Kurhaluk, Oleksandr Lukash, Valentina Nosar, Alla G Portnychenko, Volodymyr Portnychenko, Magdalena Wszedybyl-Winklewska, Pawel J Winklewski
High-altitude intolerance, and consequently high-altitude sickness is difficult to predict. Liver is essential organ in glucose and lipid metabolism, and may play key role in the adaptation to high altitude. In response to extreme high altitude, mitochondrial respiration exhibits changes in substrate metabolism, mitochondrial electron transport chain activity and respiratory coupling. We determined the cobalt chloride (CoCl2) effects on liver mitochondrial plasticity and oxygen uptake in rats with low (LR) and high (HR) resistance to extreme hypobaric hypoxia...
January 25, 2019: Canadian Journal of Physiology and Pharmacology
Antoinette Oliveira Blackman, José Sobral Neto, Melchior Luiz Lima, Tânia Maria Andrade Rodrigues, Otoni Moreira Gomes
Imbalance in ventricular repolarization parameters are related to increased risk of severe arrhythmia and sudden cardiac death. There is limited research regarding markers to detect patients at risk in this early stage. We aimed to assess the influence of grade I left ventricular diastolic dysfunction on repolarization parameters in asymptomatic patients. Ambulatory patients with grade I left ventricular diastolic dysfunction were studied and compared with a control group. We assessed: the QT dispersion circadian variation, heart rate variability in the time and frequency domains and dynamics of QT using a 12-lead Holter...
January 24, 2019: Canadian Journal of Physiology and Pharmacology
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