{"title":"Changes in renal vessels associated with long-term administration of angiotensin converting enzyme inhibitor in Zucker fatty rats.","authors":"Kazushige Nakanishi, Yohko Nagai, Tatsuo Akimoto, Nobuaki Yamanaka","doi":"10.1540/jsmr.53.20","DOIUrl":"https://doi.org/10.1540/jsmr.53.20","url":null,"abstract":"<p><p>Background Recently, we showed that long-term angiotensin receptor blocker (ARB) administration induced unusual proliferative changes in smooth muscle cells (SMCs) of afferent arterioles of the kidneys of Zucker fatty rats (ZFRs). In this study, we investigated renal afferent arteriolar changes induced by the long-term administration of an angiotensin converting enzyme inhibitor (ACEI) in ZFRs. Materials and Methods Fourteen 6-week-old male ZFRs were divided into two groups (n=14): the ZFR+ACEI group (n=6) was fed a standard diet containing ACEI (Enalapril, 2 mg/kg/day), and the ZFR control group (n=8) for 12 weeks. Blood pressure and proteinuria were examined and morphological studies on kidneys were performed. Results Remarkable proliferative changes in the afferent arteriolar SMCs were frequently observed in the group given ACEI; (66.1 ± 12.9%) compared with the control group (1.77 ± 1.56%, P<0.001). Conclusions It was indicated that long-term ACEI administration induced unusual proliferative changes in SMCs in afferent arterioles of ZFRs. These changes could reduce intraglomerular pressure by narrowing the lumens of afferent arterioles, but they could cause irreversible damage to the arterioles.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"53 0","pages":"20-30"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.53.20","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34783241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of prostatic interstitial cells in prostate motility.","authors":"Richard J Lang, Hikaru Hashitani","doi":"10.1540/jsmr.53.57","DOIUrl":"https://doi.org/10.1540/jsmr.53.57","url":null,"abstract":"<p><p>The prostate is a gland whose secretions contribute to the seminal fluids ejaculated upon activation of autonomic sympathetic nerves. In elder males, the prostate undergoes an increase in stroma mass and myogenic tone, leading to benign prostatic hyperplasia that occludes the proximal urethra and the presentation of various lower urinary tract symptoms that decrease their quality of life. This review summarises the role of prostatic interstitial cells (PICs) in the generation of the spontaneous tone in the prostate. It presents current knowledge of the role of Ca<sup>2+</sup> plays in PIC pacemaking, as well as the mechanisms by which this spontaneous activity triggers slow wave generation and stromal contraction. PICs display a small T-type Ca<sup>2+</sup> current (I<sub>CaT</sub>) and a large L-type Ca<sup>2+</sup> current (I<sub>CaL</sub>). In contrast to other interstitial cells in the urinary and gastrointestinal tracts, spontaneous Ca<sup>2+</sup> signalling in PICs is uniquely dependent on Ca<sup>2+</sup> influx through I<sub>CaL</sub> channels. A model of prostatic pacemaking is presented describing how I<sub>CaL</sub> can be triggered by an initial membrane depolarization evoked upon the selective opening of Ca<sup>2+</sup>-activated Cl<sup>-</sup> channels by Ca<sup>2+</sup> flowing only through I<sub>CaT</sub> channels. The resulting current flow through I<sub>CaL</sub> results in release of Ca<sup>2+</sup> from internal stores and the summation of Cl<sup>-</sup>-selective spontaneous transient depolarizations (STDs) to form pacemaker potentials that propagate passively into the prostatic stroma to evoke regenerative action potentials and excitation-contraction coupling.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"53 0","pages":"57-72"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.53.57","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35121297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanisms underlying the pathogenesis of hyper-contractility of bronchial smooth muscle in allergic asthma.","authors":"Hiroyasu Sakai, Wataru Suto, Yuki Kai, Yoshihiko Chiba","doi":"10.1540/jsmr.53.37","DOIUrl":"https://doi.org/10.1540/jsmr.53.37","url":null,"abstract":"<p><p>Airway hyperresponsiveness (AHR) and inflammation are key pathophysiological features of asthma. Enhanced contraction of bronchial smooth muscle (BSM) is one of the causes of the AHR. It is thus important for development of asthma therapy to understand the change in the contractile signaling of airway smooth muscle cells associated with the AHR. In addition to the Ca<sup>2+</sup>-mediated phosphorylation of myosin light chain (MLC), contractile agonists also enhance MLC phosphorylation level, Ca<sup>2+</sup>-independently, by inactivating MLC phosphatase (MLCP), called Ca<sup>2+</sup> sensitization of contraction, in smooth muscle cells including airways. To date, involvements of RhoA/ROCKs and PKC/Ppp1r14a (also called as CPI-17) pathways in the Ca<sup>2+</sup> sensitization have been identified. Our previous studies revealed that the agonist-induced Ca<sup>2+</sup> sensitization of contraction is markedly augmented in BSMs of animal models of allergen-induced AHR. In BSMs of these animal models, the expression of RhoA and CPI-17 proteins were significantly increased, indicating that both the Ca<sup>2+</sup> sensitizing pathways are augmented. Interestingly, incubation of BSM cells with asthma-associated cytokines, such as interleukin-13 (IL-13), IL-17, and tumor necrosis factor-α (TNF-α), caused up-regulations of RhoA and CPI-17 in BSM cells of naive animals and cultured human BSM cells. In addition to the transcription factors such as STAT6 and NF-κB activated by these inflammatory cytokines, an involvement of down-regulation of miR-133a, a microRNA that negatively regulates RhoA translation, has also been suggested in the IL-13- and IL-17-induced up-regulation of RhoA. Thus, the Ca<sup>2+</sup> sensitizing pathways and the cytokine-mediated signaling including microRNAs in BSMs might be potential targets for treatment of allergic asthma, especially the AHR.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"53 0","pages":"37-47"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.53.37","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34977270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diversity and plasticity in signaling pathways that regulate smooth muscle responsiveness: Paradigms and paradoxes for the myosin phosphatase, the master regulator of smooth muscle contraction.","authors":"Masumi Eto, Toshio Kitazawa","doi":"10.1540/jsmr.53.1","DOIUrl":"https://doi.org/10.1540/jsmr.53.1","url":null,"abstract":"<p><p>A hallmark of smooth muscle cells is their ability to adapt their functions to meet temporal and chronic fluctuations in their demands. These functions include force development and growth. Understanding the mechanisms underlying the functional plasticity of smooth muscles, the major constituent of organ walls, is fundamental to elucidating pathophysiological rationales of failures of organ functions. Also, the knowledge is expected to facilitate devising innovative strategies that more precisely monitor and normalize organ functions by targeting individual smooth muscles. Evidence has established a current paradigm that the myosin light chain phosphatase (MLCP) is a master regulator of smooth muscle responsiveness to stimuli. Cellular MLCP activity is negatively and positively regulated in response to G-protein activation and cAMP/cGMP production, respectively, through the MYPT1 regulatory subunit and an endogenous inhibitor protein named CPI-17. In this article we review the outcomes from two decade of research on the CPI-17 signaling and discuss emerging paradoxes in the view of signaling pathways regulating smooth muscle functions through MLCP.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"53 0","pages":"1-19"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.53.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34783242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nataliya A Kuzubova, Elena S Lebedeva, Olga N Titova, Anatoliy N Fedin, Ivetta V Dvorakovskaya
{"title":"Role of mast cells in bronchial contraction in nonallergic obstructive lung pathology.","authors":"Nataliya A Kuzubova, Elena S Lebedeva, Olga N Titova, Anatoliy N Fedin, Ivetta V Dvorakovskaya","doi":"10.1540/jsmr.53.90","DOIUrl":"https://doi.org/10.1540/jsmr.53.90","url":null,"abstract":"<p><p>The role of mast cells in contractile bronchial smooth muscle activity has been evaluated in a model of chronic obstructive pulmonary disease induced in rats that were intermittently exposed to nitrogen dioxide (NO<sub>2</sub>) for 60 days. Starting from the 31st day, one group of rats inhaled sodium cromoglycate before exposure to NO<sub>2</sub> to stabilize mast cell membranes. The second group (control) was not treated. Isometric smooth muscle contraction was analysed in isolated bronchial samples in response to nerve and smooth muscle stimulation. Histological analysis revealed large numbers of mast cells in lung tissue of COPD model rats. The inhibition of mast cell degranulation by sodium cromoglycate prevented the development of nerve-stimulated bronchial smooth muscle hyperactivity in COPD model rats. Histamine or adenosine-induced hyperactivity on nerve stimulation was also inhibited by sodium cromoglycate in bronchial smooth muscle in both control and COPD model rats. This suggests that the mechanism of contractile activity enhancement of bronchial wall smooth muscle cells may be mediated through the activation of resident mast cells transmembrane adenosine receptors resulting in their partial degranulation, with the released histamine acting upon histamine H1-receptors which trigger reflex pathways via intramural ganglion neurons.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"53 0","pages":"90-99"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.53.90","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35373018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synthetic smooth muscle in the outer blood plexus of the rhinarium skin of Lemur catta L.","authors":"Rolf Elofsson, Ronald H H Kröger","doi":"10.1540/jsmr.53.31","DOIUrl":"https://doi.org/10.1540/jsmr.53.31","url":null,"abstract":"<p><p>The skin of the lemur nose tip (rhinarium) has arterioles in the outer vascular plexus that are endowed with an unusual coat of smooth muscle cells. Comparison with the arterioles of the same area in a number of unrelated mammalians shows that the lemur pattern is unique. The vascular smooth muscle cells belong to the synthetic type. The function of synthetic smooth muscles around the terminal vessels in the lemur rhinarium is unclear but may have additional functions beyond regulation of vessel diameter.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"53 0","pages":"31-36"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.53.31","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34783243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gastric emptying after artificial ulceration in rats: differences due to the site of the ulcer and the effects of prokinetic drugs.","authors":"Masayuki Uchida, Orie Kobayashi, Kimiko Shimizu","doi":"10.1540/jsmr.53.48","DOIUrl":"https://doi.org/10.1540/jsmr.53.48","url":null,"abstract":"<p><p>Background This study aimed to evaluate the effects of the position of an acetic acid-induced gastric ulcer and the effects of prokinetic drugs on gastric emptying. Materials and Methods Male Sprague-Dawley rats were used in this study. Acetic acid ulcers were induced either in the region between the fundus and pylorus on the anterior wall of the stomach or in the glandular region on the greater curvature of the stomach to determine whether there were regional differences in the effect of the ulcers. Gastric emptying was evaluated with a breath test using [1-<sup>13</sup>C] acetic acid. In addition, the effects of the prokinetic drugs, metoclopramide and mosapride, on gastric emptying were also evaluated. Results Acetic acid induced ulcers in the region between the fundus and pylorus on the anterior wall of the stomach significantly delayed gastric emptying as compared with control rats, but not the acetic acid induced ulcers in the glandular region on the greater curvature of the stomach. Metoclopramide and mosapride did not improve the delayed gastric emptying even at doses that enhanced gastric emptying in normal rats. Conclusion These findings show that gastric emptying is influenced by the position of the ulcer and the region between the fundus and pylorus on the anterior wall plays an important role in gastric emptying. Moreover, it was found that metoclopramide and mosapride do not improve the delayed gastric emptying caused by acetic acid ulcers induced on the anterior wall in the region between the fundus and pylorus.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"53 0","pages":"48-56"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.53.48","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35121296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Bano, Omanwar Swati, Muralidhar Kambadur, F. Mohammad
{"title":"Deterioration of epithelium mediated mechanisms in diabetic-antigen sensitized airways of guinea pigs","authors":"S. Bano, Omanwar Swati, Muralidhar Kambadur, F. Mohammad","doi":"10.1540/jsmr.52.93","DOIUrl":"https://doi.org/10.1540/jsmr.52.93","url":null,"abstract":"Background The onset of diabetes causes disruption of respiratory epithelial mediators. The present study investigates whether diabetes modifies the epithelium mediated bronchial responses in hyper-reactive airway smooth muscle (ASM) primarily through nitric oxide (NO), cyclooxygenase (COX), and epithelium derived hyperpolarizing factor (EpDHF) pathways. Methods Experimental model of guinea pigs having hyper-reactive airways with or without diabetes were developed. The responses of tracheal rings to cumulative concentrations of acetylcholine (ACh) and isoproterenol (IP) in the presence and absence of epithelium and before and after incubation with NO, K+ATP and COX inhibitors, N-(ω)-Nitro-L-arginine methyl ester (L-NAME; 100 µM), glybenclamide (10 µM) and indomethacin (100 µM) were assessed. Results In diabetic guinea pigs with hyper-reactive airways, a decrease in ACh induced bronchoconstriction was observed after epithelium removal and after incubation with L-NAME/indomethacin, suggesting damage to NO/COX pathways. Hyper-reactivity did not alter the response of trachea to ACh but affected the response to IP which was further reduced in hyper-reactive animals with diabetes. The ASM response to IP after glybenclamide treatment did not alter in hyper-reactive guinea pigs and diabetic guinea pigs with hyper-reactive airways, suggesting damage to the EpDHF pathway. Treatment with indomethacin reduced IP response in the hyper-reactive model, and did not produce any change in diabetic model with hyper-reactive airways, indicating further disruption of the COX pathway. Conclusion EpDHF pathway is damaged in hyper-reactive guinea pigs and in diabetic guinea pigs with hyper-reactive airways. Diabetes further aggravates the NO and COX mediated pathways in diabetic guinea pigs with hyper-reactive airways.","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"52 1","pages":"93 - 104"},"PeriodicalIF":0.0,"publicationDate":"2016-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.52.93","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67067469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Kurahara, K. Hiraishi, M. Sumiyoshi, Mayumi Doi, Yaopeng Hu, K. Aoyagi, Yuwen Jian, R. Inoue
{"title":"Significant contribution of TRPC6 channel-mediated Ca2+ influx to the pathogenesis of Crohn's disease fibrotic stenosis","authors":"L. Kurahara, K. Hiraishi, M. Sumiyoshi, Mayumi Doi, Yaopeng Hu, K. Aoyagi, Yuwen Jian, R. Inoue","doi":"10.1540/jsmr.52.78","DOIUrl":"https://doi.org/10.1540/jsmr.52.78","url":null,"abstract":"Intestinal fibrosis is an intractable complication of Crohn's disease (CD), and, when occurring excessively, causes severe intestinal obstruction that often necessitates surgical resection. The fibrosis is characterized by an imbalance in the turnover of extracellular matrix (ECM) components, where intestinal fibroblasts/myofibroblasts play active roles in ECM production, fibrogenesis and tissue remodeling, which eventually leads to the formation of stenotic lesions. There is however a great paucity of knowledge about how intestinal fibrosis initiates and progresses, which hampers the development of effective pharmacotherapies against CD. Recently, we explored the potential implications of transient receptor potential (TRP) channels in the pathogenesis of intestinal fibrosis, since they are known to act as cellular stress sensors/transducers affecting intracellular Ca2+ homeostasis/dynamics, and are involved in a broad spectrum of cell pathophysiology including inflammation and tissue remodeling. In this review, we will place a particular emphasis on the intestinal fibroblast/myofibroblast TRPC6 channel to discuss its modulatory effects on fibrotic responses and therapeutic potential for anti-fibrotic treatment against CD-related stenosis.","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"52 1","pages":"78 - 92"},"PeriodicalIF":0.0,"publicationDate":"2016-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.52.78","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67067455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MYPT1 isoforms expressed in HEK293T cells are differentially phosphorylated after GTPγS treatment","authors":"Simon Lin, F. Brozovich","doi":"10.1540/jsmr.52.66","DOIUrl":"https://doi.org/10.1540/jsmr.52.66","url":null,"abstract":"Agonist stimulation of smooth muscle is known to activate RhoA/Rho kinase signaling, and Rho kinase phosphorylates the myosin targeting subunit (MYPT1) of myosin light chain (MLC) phosphatase at Thr696 and Thr853, which inhibits the activity of MLC phosphatase to produce a Ca2+ independent increase in MLC phosphorylation and force (Ca2+ sensitization). Alternative mRNA splicing produces four MYPT1 isoforms, which differ by the presence or absence of a central insert (CI) and leucine zipper (LZ). This study was designed to determine if Rho kinase differentially phosphorylates MYPT1 isoforms. In HEK293T cells expressing each of the four MYPT1 isoforms, we could not detect a change in Thr853 MYPT1 phosphorylation following GTPγS treatment. However, there is differential phosphorylation of MYPT1 isoforms at Thr696; GTPγS treatment increases MYPT1 phosphorylation for the CI+LZ- and CI-LZ- MYPT1 isoforms, but not the CI+LZ+ or CI-LZ+ MYPT1 isoforms. These data could suggest that in smooth muscle Rho kinase differentially phosphorylates MYPT1 isoforms.","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"52 1","pages":"66 - 77"},"PeriodicalIF":0.0,"publicationDate":"2016-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.52.66","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67067326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}