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rho kinase and heart

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https://www.readbyqxmd.com/read/28818859/renal-denervation-suppresses-coronary-hyperconstricting-responses-after-drug-eluting-stent-implantation-in-pigs-in-vivo-through-the-kidney-brain-heart-axis
#1
Hironori Uzuka, Yasuharu Matsumoto, Kensuke Nishimiya, Kazuma Ohyama, Hideaki Suzuki, Hirokazu Amamizu, Susumu Morosawa, Michinori Hirano, Tomohiko Shindo, Yoku Kikuchi, Kiyotaka Hao, Takashi Shiroto, Kenta Ito, Jun Takahashi, Koji Fukuda, Satoshi Miyata, Yoshihito Funaki, Hatsue Ishibashi-Ueda, Satoshi Yasuda, Hiroaki Shimokawa
OBJECTIVE: Drug-eluting stent-induced coronary hyperconstricting responses remain an important issue. The adventitia harbors a variety of components that potently modulate vascular tone, including sympathetic nerve fibers (SNF) and vasa vasorum. Catheter-based renal denervation (RDN) inhibits sympathetic nerve activity. We, thus, examined whether RDN suppresses drug-eluting stent-induced coronary hyperconstricting responses, and if so, what mechanisms are involved. APPROACH AND RESULTS: Protocol 1: pigs implanted with everolimus-eluting stents into the left coronary arteries underwent coronary angiography at 1 month after implantation for assessment of coronary vasomotion and adventitial SNF formation...
August 17, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28739304/role-of-nadphox-rho-kinase-signaling-in-the-cyclosporine-nsaids-interactions-on-blood-pressure-and-baroreflexes-in-female-rats
#2
Hanan M El-Gowelli, Karim S Ibrahim, Ahmed F El-Yazbi, Mahmoud M El-Mas
AIMS: The hypertensive effect of the immunosuppressant drug cyclosporine (CSA) is paralleled, and probably triggered, by impaired arterial baroreceptor sensitivity (BRS). Here we asked if these effects of CSA are influenced by co-administration of nonsteroidal antiinflammatory drugs (NSAIDs) and if the oxidative NADPH-oxidase (NADPHox)/Rho-kinase (ROCK) pathway mediates this interaction. MATERIALS AND METHODS: Female rats were treated for 10days with CSA (25mg/kg/day), diclofenac (DIC, COX-1/COX-2 inhibitor, 1mg/kg/day), celecoxib (COX-2 inhibitor, 10mg/kg/day), or their combinations...
July 21, 2017: Life Sciences
https://www.readbyqxmd.com/read/28712398/-fasudil-attenuates-mitochondrial-injury-and-apoptosis-in-rat-model-of-myocardial-ischemia-reperfusion-injury
#3
Hongwei Ye, Guanjun Zhang, Ruiping Cao, Pinfang Kang, Zhenghong Li, Qin Gao
Objective To observe the changes of mitochondria fusion protein 2 (Mfn2) and dynamin-related protein 1 (Drp1) in the cardioprotection of fasudil, and analyze the significance. Methods Hearts isolated from male Sprague-Dawley rats were subjected to ischemia for 30 minutes (occlusion of left anterior descending artery), and continuously perfusion for 120 minutes to establish myocardial ischemia/reperfusion (I/R) injury model. The rats were divided into 3 groups: sham group, I/R group and fasudil group. The left ventricular hemodynamics were continuously recorded; lactate dehydrogenase (LDH) content was measured during reperfusion; myocardial ultrastructure was observed by electron microscopy; the protein expression of phosphorylated protein phosphatase 1 regulatory subunit 12A (p-PPP1R12A/p-MYPT1) was detected by immunohistochemistry; and the protein expressions of Mfn2, Drp1 and cleaved caspase-3 (c-caspase-3) were detected by Western blot analysis...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28679962/fibroblast-deletion-of-rock2-attenuates-cardiac-hypertrophy-fibrosis-and-diastolic-dysfunction
#4
Toru Shimizu, Nikhil Narang, Phetcharat Chen, Brian Yu, Maura Knapp, Jyothi Janardanan, John Blair, James K Liao
Although left ventricular (LV) diastolic dysfunction is often associated with hypertension, little is known regarding its underlying pathophysiological mechanism. Here, we show that the actin cytoskeletal regulator, Rho-associated coiled-coil containing kinase-2 (ROCK2), is a critical mediator of LV diastolic dysfunction. In response to angiotensin II (Ang II), mutant mice with fibroblast-specific deletion of ROCK2 (ROCK2Postn-/-) developed less LV wall thickness and fibrosis, along with improved isovolumetric relaxation...
July 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28657365/acute-hypobaric-hypoxia-augments-rock2-protein-level-and-activity
#5
Priyanka Pandey, Sangeeta Kumari, Zahara Ali, Ma Qadar Pasha
AIM: Rho kinase activation plays an important role in hypoxic pulmonary vasoconstriction and increased vascular resistance. The present study investigated changes in the level and activity of rho kinase isoform 2 (ROCK2) under acute hypobaric hypoxia exposure. For this, Wistar rats were taken as the model organism. MATERIALS AND METHODS: Fifteen male Wistar rats (4-6 week old, 250 grams) were normalized with the surrounding environment by providing a 12/12 hour day and night acclimatization cycle...
June 28, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28589995/trans-polydatin-protects-the-mouse-heart-against-ischemia-reperfusion-injury-via-inhibition-of-the-renin-angiotensin-system-ras-and-rho-kinase-rock-activity
#6
Dong Ming, Liao Songyan, Chen Yawen, Zheng Na, Ma Jing, Xiao Zhaowen, Liu Ye, Ding Wa, Liu Jie
BACKGROUND: Recent studies highlighted the protective benefits of a Chinese herb extract from polygonum cuspidatum, trans-polydatin, on cardiac disease. We investigated the therapeutic effect of trans-polydatin on myocardial ischemia/reperfusion (IR) injury and the underlying mechanisms related to the renin-angiotensin system (RAS) and RhoA kinase (ROCK) pathway. METHODS AND RESULTS: Experiments were performed on neonatal rats' ventricular myocytes that were subjected to hypoxia-reoxygenation (simulated IR, SIR) and on adult mice which were subjected to left anterior descending coronary artery occlusion for 45 min followed by a one-week reperfusion...
June 7, 2017: Food & Function
https://www.readbyqxmd.com/read/28575410/enhanced-endothelin-1-rho-kinase-signaling-and-coronary-microvascular-dysfunction-in-hypertensive-myocardial-hypertrophy
#7
Shu-Huai Tsai, Guangrong Lu, Xin Xu, Yi Ren, Travis W Hein, Lih Kuo
Aims: Hypertensive cardiac hypertrophy is associated with reduced coronary flow reserve, but its impact on coronary flow regulation and vasomotor function remains incompletely understood and requires further investigation. Methods and results: Left ventricular hypertrophy was induced in mice by transverse aortic coarctation (TAC) for 4 weeks. The left coronary artery blood velocity (LCABV) and myocardium lactate level were measured following the metabolic activation by isoproterenol...
May 29, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28484504/effect-of-qskl-on-mapk-and-rhoa-pathways-in-a-rat-model-of-heart-failure
#8
Kai Xia, Qiyan Wang, Chun Li, Zifan Zeng, Yong Wang, Wei Wang
Qishenkeli (QSKL) is one of the Chinese medicine formulae for treating heart failure and has been shown to have an antifibrotic effect. However, the mechanism of its therapeutic effects remains unclear. In this study, we aimed to explore whether QSKL could exert an antifibrotic effect by attenuating ras homolog family member A (RhoA) and mitogen activated protein kinase (MAPK) pathways. Rats were randomly divided into sham group, model group, QSKL group, and positive control group. Heart failure was induced by ligation of the left ventricle anterior descending artery...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28416371/modulation-by-nadph-oxidase-of-the-chronic-cardiovascular-and-autonomic-interaction-between-cyclosporine-and-nsaids-in-female-rats
#9
Ahmed F El-Yazbi, Karim S Ibrahim, Hanan M El-Gowelli, Nevine M El-Deeb, Mahmoud M El-Mas
Cyclosporine (CSA) and nonsteroidal antiinflammatory drugs (NSAIDs) are used together to manage arthritic disorders with an immune component. Previous reports showed contrasting effects for NSAIDs on CSA nephrotoxicity and acute elevations in blood pressure. Both effects were ameliorated or exaggerated after selective cyclooxygenase-2 (COX2) and nonselective COX inhibition, respectively. Here we investigated: (i) the interaction of CSA with NSAIDs possessing variable COX1/COX2 selectivities on hemodynamic, left ventricular (LV) and cardiac autonomic and histologic profiles, and (ii) role of NADPH-oxidase (NOX)/Rho-kinase (ROCK) pathway in the interaction...
April 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28400117/phosphatidylinositol-3-kinase-inhibition-induces-vasodilator-effect-of-sevoflurane-via-reduction-of-rho-kinase-activity
#10
Yasunori Miyamoto, Guo-Gang Feng, Shiho Satomi, Katsuya Tanaka, Yoshihiro Fujiwara, Hiroyuki Kinoshita
AIMS: This study was aimed to examine whether a volatile anesthetic sevoflurane in clinical doses reduces vasoconstriction under the inhibition of phosphatidylinositol 3-kinase (PI3K) in the rat and human arteries and whether the intravenous administration of the PI3K inhibitor decreases blood pressure in rats under the sevoflurane inhalation. MATERIALS AND METHODS: Rat arteries (n=5-6) and human omental arteries (n=5-6) were subjected to isometric force recordings and western immunoblotting for Rho kinase, mitogen-activated protein kinase, and protein kinase C...
May 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28183205/inhibition-of-rho-kinase-protects-from-ischaemia-reperfusion-injury-via-regulation-of-arginase-activity-and-nitric-oxide-synthase-in-type-1-diabetes
#11
Yahor Tratsiakovich, Attila Kiss, Adrian T Gonon, Jiangning Yang, Per-Ove Sjöquist, John Pernow
AIM: RhoA/Rho-associated kinase and arginase are implicated in vascular complications in diabetes. This study investigated whether RhoA/Rho-associated kinase and arginase inhibition protect from myocardial ischaemia-reperfusion injury in type 1 diabetes and the mechanisms behind these effects. METHODS: Rats with streptozotocin-induced type 1 diabetes and non-diabetic rats were subjected to 30 min myocardial ischaemia and 2 h reperfusion after being randomized to treatment with (1) saline, (2) RhoA/Rho-associated kinase inhibitor hydroxyfasudil, (3) nitric oxide synthase inhibitor N(G)-monomethyl-l-arginine monoacetate followed by hydroxyfasudil, (4) arginase inhibitor N-omega-hydroxy-nor-l-arginine, (5) N(G)-monomethyl-l-arginine monoacetate followed by N-omega-hydroxy-nor-l-arginine or (6) N(G)-monomethyl-l-arginine monoacetate given intravenous before ischaemia...
May 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28165252/cocktail-of-superoxide-dismutase-and-fasudil-encapsulated-in-targeted-liposomes-slows-pah-progression-at-a-reduced-dosing-frequency
#12
Nilesh Gupta, Jahidur Rashid, Eva Nozik-Grayck, Ivan F McMurtry, Kurt R Stenmark, Fakhrul Ahsan
Currently, two or more pulmonary vasodilators are used to treat pulmonary arterial hypertension (PAH), but conventional vasodilators alone cannot reverse disease progression. In this study, we tested the hypothesis that a combination therapy comprising a vasodilator plus a therapeutic agent that slows pulmonary arterial remodeling and right heart hypertrophy is an efficacious alternative to current vasodilator-based PAH therapy. Thus, we encapsulated a cocktail of superoxide dismutase (SOD), a superoxide scavenger, and fasudil, a specific rho-kinase inhibitor, into a liposomal formulation equipped with a homing peptide, CAR...
March 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28131915/rock1-p53-noxa-signaling-mediates-cardiomyocyte-apoptosis-in-response-to-high-glucose-in-vitro-and-vivo
#13
Dongmei Su, Lina Guan, Qianqian Gao, Qian Li, Cuige Shi, Yi Liu, Lei Sun, Cailing Lu, Xu Ma, Jing Zhao
Gestational diabetes mellitus is a risk factor for congenital heart defects; however, the molecular basis of the congenital heart anomalies remains obscure. Previous reports showed a positive correlation between abnormal cardiomyocyte apoptosis and ventricular wall thinness, one type of congenital heart anomaly. This work explored the expression pattern and molecular mechanism of the Rho-associated coiled-coil containing protein kinase 1 (ROCK1) gene in cardiomyocyte apoptosis and genesis of ventricular wall thinness...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28003226/canstatin-stimulates-migration-of-rat-cardiac-fibroblasts-via-secretion-of-matrix-metalloproteinase-2
#14
Muneyoshi Okada, Naoki Murata, Hideyuki Yamawaki
Type IV collagen, a nonfibrillar type, is ubiquitously expressed in the basement membrane around cardiomyocytes. Canstatin, a cleaved product of α2 chain of type IV collagen, is an antiangiogenic factor. Because it has not been clarified whether canstatin exerts other biological activities in heart, we investigated the effects of canstatin on adult rat cardiac fibroblasts. Cell migration was determined by Boyden chamber assay. Western blotting was performed to detect secretion of matrix metalloproteinase-2 (MMP-2) and MMP-9 and phosphorylation of extracellular signal-regulated kinase (ERK)...
March 1, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27998869/-role-of-autophagy-in-fasudil-induced-rho-kinase-inhibition-for-protection-against-myocardial-ischemia-reperfusion-injury-in-rats
#15
Hong-Wei Ye, Ting-Ting Fang, Xiao-Yu Gu, Ya Wang, Guang-Yu Zhu, Ying Yu, Qin Gao
OBJECTIVE: To investigate the changes of autophagy in ischemic myocardium of rats treated with fasudil for inhibiting Rho kinase. METHODS: The hearts isolated from male Sprague-Dawley rats were subjected to 30 min of occlusion of the left anterior descending artery followed by 120 min of reperfusion with or without treatment with fasudil or fasudil+Wort. The left ventricular hemodynamics were continuously recorded, and the coronary effluent was collected during the reperfusion to determine lactate dehydrogenase (LDH) levels...
December 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27780848/sucrose-nonfermenting-related-kinase-enzyme-mediated-rho-associated-kinase-signaling-is-responsible-for-cardiac-function
#16
Stephanie M Cossette, Vijesh J Bhute, Xiaoping Bao, Leanne M Harmann, Mark A Horswill, Indranil Sinha, Adam Gastonguay, Shabnam Pooya, Michelle Bordas, Suresh N Kumar, Shama P Mirza, Sean P Palecek, Jennifer L Strande, Ramani Ramchandran
BACKGROUND: Cardiac metabolism is critical for the functioning of the heart, and disturbance in this homeostasis is likely to influence cardiac disorders or cardiomyopathy. Our laboratory has previously shown that SNRK (sucrose nonfermenting related kinase) enzyme, which belongs to the AMPK (adenosine monophosphate-activated kinase) family, was essential for cardiac metabolism in mammals. Snrk global homozygous knockout (KO) mice die at postnatal day 0, and conditional deletion of Snrk in cardiomyocytes (Snrk cmcKO) leads to cardiac failure and death by 8 to 10 months...
December 2016: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/27753928/os-05-03-decreased-rho-kinase-based-calcium-sensitization-in-hypertensive-ren-2-transgenic-rats-tgr
#17
Josef Zicha, Michal Behuliak, Ivana Vaneckova
OBJECTIVE: Comparing BP response to Ca channel opener BAY K8644 prior and after Rho kinase inhibition we demonstrated lowered calcium sensitization in spontaneously hypertensive rats (SHR), although BP response of intact SHR to Rho kinase inhibitor fasudil was enhanced (Behuliak et al. J Hypertens 31:2025,2013). The aim of the present study was to evaluate calcium sensitization in hypertensive TGR and their normotensive HanSD controls using the same methods. We also tried to elucidate the interference of baroreflex-activated sympathetic activity with BP response to fasudil...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27672026/central-angiotensin-ii-increases-blood-pressure-and-sympathetic-outflow-via-rho-kinase-activation-in-conscious-rabbits
#18
Peter R Pellegrino, Alicia M Schiller, Karla K V Haack, Irving H Zucker
Elevated sympathetic tone and activation of the renin-angiotensin system are pathophysiologic hallmarks of hypertension, and the interactions between these systems are particularly deleterious. The importance of Rho kinase as a mediator of the effects of angiotensin-II (AngII) in the periphery is clear, but the role of Rho kinase in sympathoexcitation caused by central AngII is not well established. We hypothesized that AngII mediates its effects in the brain by the activation of the RhoA/Rho kinase pathway...
November 2016: Hypertension
https://www.readbyqxmd.com/read/27643321/os-05-03-decreased-rho-kinase-based-calcium-sensitization-in-hypertensive-ren-2-transgenic-rats-tgr
#19
Josef Zicha, Michal Behuliak, Ivana Vaneckova
OBJECTIVE: Comparing BP response to Ca channel opener BAY K8644 prior and after Rho kinase inhibition we demonstrated lowered calcium sensitization in spontaneously hypertensive rats (SHR), although BP response of intact SHR to Rho kinase inhibitor fasudil was enhanced (Behuliak et al. J Hypertens 31:2025,2013). The aim of the present study was to evaluate calcium sensitization in hypertensive TGR and their normotensive HanSD controls using the same methods. We also tried to elucidate the interference of baroreflex-activated sympathetic activity with BP response to fasudil...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27581840/liraglutide-prevents-and-reverses-monocrotaline-induced-pulmonary-arterial-hypertension-by-suppressing-et-1-and-enhancing-enos-sgc-pkg-pathways
#20
Mei-Yueh Lee, Kun-Bow Tsai, Jong-Hau Hsu, Shyi-Jang Shin, Jiunn-Ren Wu, Jwu-Lai Yeh
Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is widely used to treat diabetes. However, its effect on pulmonary arterial hypertension (PAH) is unknown. In this study, we investigated its effects on rats with monocrotaline (MCT)-induced PAH and mechanisms on rat pulmonary artery smooth muscle cells (PASMCs). Liraglutide was investigated for both prevention and treatment of MCT-induced PAH. The hemodynamic and body weight changes, right heart hypertrophy, lung morphology, immune-reactivity of endothelial nitric oxide synthase (eNOS), endothelin-1 and cyclic guanosine monophosphate (cGMP) levels, protein expressions of eNOS, soluble guanylyl cyclase (sGCα), protein kinase G (PKG) and Rho kinase (ROCK) II pathway were measured in both in vivo and in vitro...
2016: Scientific Reports
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