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KCl and rho kinase

Qingfeng Yu, Christian Gratzke, Yiming Wang, Annika Herlemann, Frank Strittmatter, Beata Rutz, Christian G Stief, Martin Hennenberg
Alpha1-adrenoceptors induce prostate smooth muscle contraction, and hold a prominent role for pathophysiology and therapy of lower urinary tract symptoms in benign prostatic hyperplasia. G protein-coupled receptors are regulated by posttranslational regulation, including phosphorylation by G protein-coupled receptor kinases 2 and 3 (GRK2/3). Although posttranslational adrenoceptor regulation has been recently suggested to occur in the prostate, this is still marginally understood. With the newly developed CMPD101, a small molecule with assumed specificity for GRK2/3 is now available...
April 23, 2018: European Journal of Pharmacology
Hae Jin Kim, Hae Young Yoo, Yin Hua Zhang, Woo Kyung Kim, Sung Joon Kim
Plumbagin, a hydroxy 1,4-naphthoquinone compound from plant metabolites, exhibits anticancer, antibacterial, and antifungal activities via modulating various signaling molecules. However, its effects on vascular functions are rarely studied except in pulmonary and coronary arteries where NADPH oxidase (NOX) inhibition was suggested as a mechanism. Here we investigate the effects of plumbagin on the contractility of skeletal artery (deep femoral artery, DFA), mesenteric artery (MA) and renal artery (RA) in rats...
November 2017: Korean Journal of Physiology & Pharmacology
Zhong-Yan Zhou, Jia-Qi Xu, Wai-Rong Zhao, Xin-Lin Chen, Yu Jin, Nuo Tang, Jing-Yi Tang
Ferulic acid, a natural ingredient presents in several Chinese Materia Medica such as Radix Angelicae Sinensis, has been identified as an important multifunctional and physiologically active small molecule. However, its pharmacological activity in different blood vessel types and underlying mechanisms are unclear. The present study was to investigate the vascular reactivity and the possible action mechanism of FA on aorta, small mesenteric arteries and coronary arteries isolated from Wistar rats. We found FA dose-dependently relieved the contraction of aorta, small mesenteric arteries and coronary arteries induced by different contractors, U46619, phenylephrine (Phe) and KCl...
November 15, 2017: European Journal of Pharmacology
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...
August 18, 2016: BMC Anesthesiology
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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