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KCl and rho kinase

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https://www.readbyqxmd.com/read/27538808/sevoflurane-and-isoflurane-inhibit-kcl-induced-class-ii-phosphoinositide-3-kinase-%C3%AE-subunit-mediated-vasoconstriction-in-rat-aorta
#1
Shaozhong Yang, Qi Wu, Shanshan Huang, Zi Wang, Feng Qi
BACKGROUND: Class II phosphoinositide 3-kinase α-isoform (PI3K-C2α) is involved in regulating KCl-induced vascular smooth muscle contraction. The current study was to investigate the effects of sevoflurane (SEVO) and isoflurane (ISO) on KCl-elicited PI3KC2α mediated vasoconstriction in rat aortic smooth muscle. METHODS: Isometric force, in the absence or presence of SEVO or ISO (1 ~ 3 minimum alveolar concentration, MAC), PI3K inhibitor LY294002, Rho kinase inhibitor Y27632, and membrane translocation of PI3K-p85, PI3K-C2α, Rho kinase (Rock II), or phosphorylation of MYPT1/Thr853, MYPT1/Thr696, CPI-17/Thr38 and MLC in response to KCl (60 mM) was measured by using isometric force transducer and western blotting analysis, respectively...
2016: BMC Anesthesiology
https://www.readbyqxmd.com/read/27508567/-op-8c-02-senescence-increases-vascular-smooth-muscle-contractions-through-increased-rho-kinase-activity-in-female-mouse-aorta
#2
S Novella, X Vidal-Gómez, I Pérez-Monzó, A Mompeón, D Pérez-Cremades, A P Dantás, G Segarra, C Hermenegildo, P Medina
OBJECTIVE: In vascular smooth muscle the Rho signaling pathway is highly activated in a variety of vascular diseases. Our aim was to check the involvement of Rho kinase (ROCK) on the increased vascular contractions induced by ageing in female mouse aorta. DESIGN AND METHOD: Female senescence-accelerated mice (SAMP8, n = 21) or the control, SAM-resistant (SAMR1, n = 21), were divided in three groups: 3-, 6-, and 10-months old. Vascular rings (4 mm long) from thoracic aorta were mounted for isometric recording of tension...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27432870/heterogeneous-impact-of-rock2-on-carotid-and-cerebrovascular-function
#3
T Michael De Silva, Dale A Kinzenbaw, Mary L Modrick, Lindsey D Reinhardt, Frank M Faraci
Rho kinase (ROCK) has been implicated in physiological and pathophysiological processes, including regulation of vascular function. ROCK signaling is thought to be a critical contributor to cardiovascular disease, including hypertension and effects of angiotensin II (Ang II). Two isoforms of ROCK (1 and 2) have been identified and are expressed in vascular cells. In this study, we examined the importance of ROCK2 in relation to vessel function using several models and a novel inhibitor of ROCK2. First, incubation of carotid arteries with the direct RhoA activator CN-03 or Ang II impaired endothelium-dependent relaxation by ≈40% to 50% (P<0...
September 2016: Hypertension
https://www.readbyqxmd.com/read/27346833/fasudil-evokes-vasodilatation-of-rat-mesenteric-vascular-bed-via-ca-2-channels-and-rho-rock-pathway
#4
Yu-Cai Chen, Tian-Yi Yuan, Hui-Fang Zhang, Dan-Shu Wang, Zi-Ran Niu, Li Li, Lian-Hua Fang, Guan-Hua Du
As a Rho kinase (ROCK) inhibitor, fasudil has been used in clinical trials of several cardiovascular diseases. This study was to investigate the vasorelaxant effect of fasudil on resistance arterial rings including mesenteric, renal, ventral tail and basilar artery. We also examined the potential mechanisms of its vasodilatory action using mesenteric artery rings. A DMT multiwire myograph system was used to test the tension of isolated small arteries. K(+) channel blockers, NO-cGMP pathway blockers and Ca(2+)-free physiological salt solution (PSS) were employed to verify the underlying mechanisms...
October 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27199130/pregnancy-associated-adaptations-in-ca2-i-dependent-and-ca2-sensitization-mechanisms-of-venous-contraction-implications-in-pregnancy-related-venous-disorders
#5
Yin Xia, Raouf A Khalil
Pregnancy is associated with significant adaptations in the maternal hemodynamics and arterial circulation, but the changes in the venous mechanisms during pregnancy are less clear. We hypothesized that pregnancy is associated with alterations in venous function, intracellular free Ca(2+) concentration ([Ca(2+)]i), and Ca(2+)-dependent mechanisms of venous contraction. Circular segments of inferior vena cava (IVC) from virgin and late pregnant (Preg, day 19) Sprague-Dawley rats were suspended between two hooks, labeled with fura-2, and placed in a cuvet inside a spectrofluorometer for simultaneous measurement of contraction and [Ca(2+)]i (fura-2 340/380 ratio)...
June 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27124860/mirabegron-causes-relaxation-of-human-and-rat-corpus-cavernosum-could-it-be-a-potential-therapy-for-erectile-dysfunction
#6
Serap Gur, Taylor Peak, Faysal A Yafi, Philip J Kadowitz, Suresh C Sikka, Wayne J G Hellstrom
OBJECTIVE: To examine the effects of mirabegron, a selective β3 -adrenoceptor agonist that has recently been approved for the treatment of overactive bladder (OAB), on erectile function. Stimulation of β3 -adrenoceptors localised in cavernosal smooth muscle cells may play a physiological role in mediating penile erection, and offer a beneficial pharmacological action for patients who have OAB and erectile dysfunction (ED). MATERIALS AND METHODS: Corpus cavernosal (CC) specimens were obtained from patients with ED and Peyronie's disease undergoing penile prosthesis implantation...
September 2016: BJU International
https://www.readbyqxmd.com/read/26610064/atorvastatin-acutely-reduces-the-reactivity-to-spasmogens-in-rat-aorta-implication-of-the-inhibition-of-geranylgeranylation-and-mypt-1-phosphorylation
#7
Fatoş İlkay Alp Yildirim, Deniz Kaleli Durman, Eda Aypar, Mustafa Ark, Osman Özdemir, Birsel Sönmez Uydeş Doğan
Statins are known to display benefits in various diseases independently from their cholesterol lowering properties. In this study, we investigated the acute effects of atorvastatin on vascular reactivity to various spasmogens in isolated rat aorta. The responses to noradrenaline (NA, 10(-8) -10(-4) m), endothelin-1 (ET-1, 10(-10) -10(-7) m), and potassium chloride (KCl, 10-100 mm) were evaluated in aortic rings pretreated with atorvastatin (10(-7) -10(-4) m, 30 min). To verify the mechanism of action, the effects of atorvastatin were studied in the presence of cholesterol precursor, mevalonate (10(-2) m, 45 min), mevalonate-derived isoprenoids, namely geranylgeranyl pyrophosphate (GGPP, 5 × 10(-6) m, 30 min) and farnesyl pyrophosphate (FPP, 5 × 10(-6) m, 30 min), and in the absence of endothelium...
April 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/26169563/effects-of-ethanol-on-rhoa-rho-kinase-mediated-calcium-sensitization-in-mouse-lung-parenchymal-tissue
#8
Fatma Aydinoglu, Olcay Ergurhan Kiroglu, Erhan Astarci, Ebru Balli, Nuran Ogulener
Calcium sensitization by the RhoA/Rho-kinase (ROCK) pathway contributes to the contraction in smooth muscle. Contractile stimuli can sensitize myosin to Ca(2+) by activating RhoA/Rho-kinase that inhibits myosin light chain phosphatase activity. The present study was aimed at investigating the possible involvement of RhoA/Rho-kinase pathway in contractile responses to agonist (phenylephrine) and depolarizing (KCl) of mouse lung parenchymal tissues. Also, we investigated the effect of ethanol on RhoA/Rho-kinase pathway...
October 5, 2015: European Journal of Pharmacology
https://www.readbyqxmd.com/read/25956403/%C3%AE-3-adrenoceptor-mediated-relaxation-of-rat-and-human-urinary-bladder-roles-of-bkca-channels-and-rho-kinase
#9
Hana Cernecka, Kim Kersten, Harm Maarsingh, Carolina R Elzinga, Igle Jan de Jong, Cees Korstanje, Martin C Michel, Martina Schmidt
Previous studies suggest that the large-conductance Ca(2+)-activated K(+) (BKCa) channel and Rho-kinase play major roles in the control of urinary bladder tone. Here, we investigated their involvement in β-adrenoceptor (AR)-mediated relaxation of rat and human bladder. Concentration-response curves of isoprenaline and mirabegron-induced bladder relaxation were generated against passive tension and KCl- and carbachol-induced tone, in the absence or presence of the BKCa channel inhibitor iberiotoxin (100 nM) or the Rho-kinase inhibitor Y27,632 (1 μM)...
July 2015: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/25860025/chronic-ouabain-treatment-induces-rho-kinase-activation
#10
Aysun Ozdemir, Gürkan Şahan, Ayşegül Demirtaş, Eda Aypar, Gürkan Gözübüyük, Nilüfer Nermin Turan, Mustafa Ark
Ouabain is an endogenous Na(+)/K(+)-ATPase inhibitor whose chronic administration induces hypertension. Endogenous ouabain levels increase in human essential hypertension. On the other hand, Rho/Rho kinase (ROCK) pathway has been implicated in various animal models of hypertension. In the current work, we evaluated the possible involvement of Rho kinase in ouabain-induced hypertension. Ouabain was administered daily (20 µg/kg, i.p.) to Wistar rats for 6 weeks. After the ouabain treatment, we evaluated the possible changes in vascular responses to KCl and phenylephrine alone and in the presence of Rho kinase inhibitor Y27632...
October 2015: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/25761652/28-day-hindlimb-unweighting-reduces-expression-of-rho-kinase-and-inhibits-its-effects-in-femoral-artery-of-rat
#11
Zhong-Chao Wang, Huan Liu, Yun-Gang Bai, Jin-Wen Yu, Hai-Jun Zhang, Yao-Ping Cheng, Jun-Xiang Bao, Xin-Ling Ren, Hong-Zhe Ma, Jin Ma
Previous studies have demonstrated inconsistent roles of Rho kinase (ROCK) in the decreased vasoconstriction of rat hindquarter vessels induced by hindlimb unweighting (HU). The present study was designed to determine the unclear role of ROCK in the mediation of HU-induced decreased femoral arterial vasoconstriction. 28-day HU rat was adopted as the animal model. With or without Y-27632, a ROCK inhibitor, isometric force of femoral artery was measured. The expression of ROCK and its effects on downstream targets were also examined...
June 2015: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/25711469/hydrogen-sulphide-induces-vasoconstriction-of-rat-coronary-artery-via-activation-of-ca-2-influx
#12
N-N Ping, S Li, Y-N Mi, L Cao, Y-X Cao
AIM: Hydrogen sulphide (H2S) exhibits a dual modulation of isolated artery tension. This study investigated the vasoconstrictive effect of sulphur sodium hydride (NaHS), a donor of gaseous H2S, on rat coronary artery. METHODS: The contractile response of isolated arteries was recorded using a wire myograph. Fluo-3/AM was used to load vascular smooth muscle, and intracellular calcium was determined using confocal laser microscopy. The protein expression of Rho kinase was examined using Western blot...
May 2015: Acta Physiologica
https://www.readbyqxmd.com/read/25593287/spaceflight-on-the-bion-m1-biosatellite-alters-cerebral-artery-vasomotor-and-mechanical-properties-in-mice
#13
Svetlana I Sofronova, Olga S Tarasova, Dina Gaynullina, Anna A Borzykh, Bradley J Behnke, John N Stabley, Danielle J McCullough, Joshua J Maraj, Mina Hanna, Judy M Muller-Delp, Olga L Vinogradova, Michael D Delp
Conditions during spaceflight, such as the loss of the head-to-foot gravity vector, are thought to potentially alter cerebral blood flow and vascular resistance. The purpose of the present study was to determine the effects of long-term spaceflight on the functional, mechanical, and structural properties of cerebral arteries. Male C57BL/6N mice were flown 30 days in a Bion-M1 biosatellite. Basilar arteries isolated from spaceflight (SF) (n = 6), habitat control (HC) (n = 6), and vivarium control (VC) (n = 16) mice were used for in vitro functional and mechanical testing and histological structural analysis...
April 1, 2015: Journal of Applied Physiology
https://www.readbyqxmd.com/read/25086815/vasodilatory-effect-of-a-novel-rho-kinase-inhibitor-dl0805-2-on-the-rat-mesenteric-artery-and-its-potential-mechanisms
#14
Tian-Yi Yuan, Yu Yan, Yu-Jie Wu, Xiao-Na Xu, Li Li, Xiao-Zhen Jiao, Ping Xie, Lian-Hua Fang, Guan-Hua Du
PURPOSE: In the present study, we investigated the vasodilatory effect of a novel scaffold Rho-kinase inhibitor, DL0805-2, on isolated rat arterial rings including mesenteric, ventral tail, and renal arteries. We also examined the potential mechanisms of its vasodilatory action using mesenteric artery rings. METHODS: A DMT multiwire myograph system was used to test the tension of isolated small arteries. Several drugs were employed to verify the underlying mechanisms...
October 2014: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/24951589/myosin-phosphatase-target-subunit-1-mypt1-regulates-the-contraction-and-relaxation-of-vascular-smooth-muscle-and-maintains-blood-pressure
#15
Yan-Ning Qiao, Wei-Qi He, Cai-Ping Chen, Cheng-Hai Zhang, Wei Zhao, Pei Wang, Lin Zhang, Yan-Ze Wu, Xiao Yang, Ya-Jing Peng, Ji-Min Gao, Kristine E Kamm, James T Stull, Min-Sheng Zhu
Myosin light chain phosphatase with its regulatory subunit, myosin phosphatase target subunit 1 (MYPT1) modulates Ca(2+)-dependent phosphorylation of myosin light chain by myosin light chain kinase, which is essential for smooth muscle contraction. The role of MYPT1 in vascular smooth muscle was investigated in adult MYPT1 smooth muscle specific knock-out mice. MYPT1 deletion enhanced phosphorylation of myosin regulatory light chain and contractile force in isolated mesenteric arteries treated with KCl and various vascular agonists...
August 8, 2014: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/24828018/airway-hyperresponsiveness-induced-by-repeated-esophageal-infusion-of-hcl-in-guinea-pigs
#16
Yan-Mei Cheng, Ai-Li Cao, Jian-Pu Zheng, Hong-Wei Wang, Yong-Shun Sun, Chun-Fang Liu, Bei-Bei Zhang, Yi Wang, Sheng-Liang Zhu, Da-Zheng Wu
Gastroesophageal reflux is a common disorder closely related to chronic airway diseases, such as chronic cough, asthma, chronic bronchitis, and chronic obstructive disease. Indeed, gastroesophageal acid reflux into the respiratory tract causes bronchoconstriction, but the underlying mechanisms have still not been clarified. This study aimed to elucidate functional changes of bronchial smooth muscles (BSMs) isolated from guinea pigs in an animal model of gastroesophageal reflux. The marked airway inflammation, hyperresponsiveness and remodeling were observed after guinea pigs were exposed to intraesophageal HCl infusion for 14 days...
November 2014: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/24814318/inhibitory-effect-of-rhynchophylline-on-contraction-of-cerebral-arterioles-to-endothelin-1-role-of-rho-kinase
#17
Hui-Feng Hao, Li-Mei Liu, Yu-Ying Liu, Juan Liu, Li Yan, Chun-Shui Pan, Ming-Xia Wang, Chuan-She Wang, Jing-Yu Fan, Yuan-Sheng Gao, Jing-Yan Han
ETHNOPHARMACOLOGICAL RELEVANCE: Rhynchophylline (Rhy) is a major ingredient of Uncaria rhynchophylla (UR) used to reduce blood pressure and ameliorate brain ailments. This study was to examine the role of Rho kinase (ROCK) in the inhibition of Rhy on contraction of cerebral arterioles caused by endothelin 1 (ET-1). MATERIALS AND METHODS: Cerebral arterioles of male Wistar rats were constricted with ET-1 for 10 min followed by perfusion of Rhy for 20 min. Changes in the diameters of the arterioles were recorded...
August 8, 2014: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/24397803/rock1-translocates-from-non-caveolar-to-caveolar-regions-upon-kcl-stimulation-in-airway-smooth-muscle
#18
B Sommer, L M Montano, J Chávez, V Carbajal, L M García-Hernandez, C Irles, A M Jiménez-Garduno, A Ortega
Airway smooth muscle (ASM) membrane depolarization through KCl opens L-type voltage dependent Ca2+ channels (Ca(v)1.2); its opening was considered the cause of KCl contraction. This substance is used to bypass intracellular second messenger pathways. It is now clear that KCl also activates RhoA/Rho kinase (ROCK) pathway. ROCK isoforms are characterized as ROCK1 and ROCK2. Because ROCK1 seems the most abundant isotype in lung, we studied its participation in KCl stimulated bovine ASM. With methyl-beta-cyclodextrin (MbetaCD) we disrupted caveolae, a membrane compartment considered as the RhoA/ROCK assembly site, and found that KCl contraction was reduced to the same extent (~26%) as Y-27632 (ROCK inhibitor) treated tissues...
2014: Physiological Research
https://www.readbyqxmd.com/read/24333215/mepivacaine-induced-contraction-involves-increased-calcium-sensitization-mediated-via-rho-kinase-and-protein-kinase-c-in-endothelium-denuded-rat-aorta
#19
Seong-Ho Ok, Seong-Chun Kwon, Jeong Yeol Han, Jongsun Yu, Il-Woo Shin, Heon-Keun Lee, Young-Kyun Chung, Mun-Jeoung Choi, Ju-Tae Sohn
Mepivacaine is an aminoamide local anesthetic that produces vasoconstriction in vivo and in vitro. The goals of this in vitro study were to determine whether mepivacaine-induced contraction involves calcium sensitization in isolated endothelium-denuded aortas, and to investigate the specific protein kinases involved. The effects of mepivacaine and potassium chloride on intracellular calcium concentrations ([Ca(2+)]i) and tension in the presence or absence of Y-27632 or GF 109203X were measured simultaneously using the acetoxymethyl ester of fura-2-loaded aortic strips...
January 15, 2014: European Journal of Pharmacology
https://www.readbyqxmd.com/read/24122009/age-dependent-contribution-of-rho-kinase-in-carbachol-induced-contraction-of-human-detrusor-smooth-muscle-in-vitro
#20
Timo Kirschstein, Chris Protzel, Katrin Porath, Tina Sellmann, Rüdiger Köhling, Oliver W Hakenberg
AIM: Activation of muscarinic receptors on the detrusor smooth muscle is followed by contraction, which involves both myosin light chain kinase (MLCK) and Rho kinase (ROCK). The aim of this study was to determine the relative contributions of MLCK and ROCK to carbachol-induced contraction of human detrusor smooth muscle in vitro. METHODS: Detrusor smooth muscle strips were prepared from the macroscopically unaffected bladder wall of patients underwent cystectomy...
January 2014: Acta Pharmacologica Sinica
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